Objectivo: Verificar a associacao entre o fenotipo da haptoglobina (Hp), uma proteina de fase agu... more Objectivo: Verificar a associacao entre o fenotipo da haptoglobina (Hp), uma proteina de fase aguda, e a concentracao plasmatica de glutationo total (GSHt) em adolescentes obesos, como forma de avaliar a capacidade antioxidante de resposta ao processo inflamatorio relacionado com a obesidade. Amostra Populacional. Foram estudados 69 adolescentes obesos, de acordo com o valor de corte de Cole, com media de idades de 11,2 ± 1,17 anos e IMC 27,4 ± 4,8. O grupo controlo e constituido por 104 adolescentes eutroficos. Metodos : A determinacao do fenotipo da haptoglobina plasmatica foi efectuada por electroforese em gel de poliacrilamida e a concentracao de GSHt foi obtida por espectrofluorimetria, usando o o-ftaldeido (OPT) como fluoroforo. Resultados: Verificou-se que a concentracao de GSHt nos adolescentes obesos e significativamente inferior a dos adolescentes do grupo controlo (mediana: 34,65 vs 48,90 μmol/L; p<0,001), estando a razao entre o GSHt e a forma oxidada do glu tationo (...
Revista Portuguesa de Endocrinologia, Diabetes e Metabolismo, 2016
The aim is to study the frequency of vertebral pain syndrome in men and women of older age groups... more The aim is to study the frequency of vertebral pain syndrome in men and women of older age groups depending on the bone mineral density (BMD). Methods: We have examined 1,934 people aged 50-89 years, among them 1697 women and 237 men. The frequency of back pain syndrome was studied depending on BMD (osteoporosis, osteopenia, and norm). BMD at all sites was measured by DXA using a Prodigy densitometer (GE). Results: The frequency of pain syndrome among older age groups is significantly higher in women compared with men (88.3% (1,499/1,697) vs 84.8% (201/237), accordingly, p = 0.01). In women of 50-89 years, with osteoporosis and no fractures in their anamnesis, pain syndrome in the thoracic and lumbar spine is significantly higher in comparison with women who have osteopenia (p = 0.01) and normal BMD (p = 0.02) and compared to men with a similar BMD state (osteoporosis; (91.8% (337/367) vs 76.2% (16/21), accordingly, p = 0.01)). The frequency of pain syndrome in the thoracic and the lumbar spine in women is associated with BMD. The presence of osteoporosis increases the risk of pain syndrome in the thoracic spine (RR = 1.27, 95%CI: 1.12-1.44, p = 0.0001). In older women, the presence of low-energy fractures significantly impacts the increasing frequency of pain in the thoracic region regardless of the BMD state. Conclusions: The frequency of pain among older age groups is significantly higher in women compared with men. In women of older age groups, the presence of low-energy fractures significantly increases the frequency of pain in the thoracic region, regardless of the state of BMD. In women 50-89 years old, with osteoporosis and no low-energy fractures, the frequency of pain in the thoracic and lumbar regions is significantly higher compared to women with osteopenia and normal BMD, as well as compared to men with a similar BMD state (osteoporosis).
Background: Since the emergence of the genus Homo, hominids have occupied a wide variety of envir... more Background: Since the emergence of the genus Homo, hominids have occupied a wide variety of environments, facing different selective pressures. Objectives: The aim this study is to compare genotype frequencies between South-West Europe and Peri-equatorial Africa in genes potentially modulators of blood pressure. Methods: The analyzed sample consisted of 325 individuals from Portugal and 226 individuals from Africa (48 from Mozambique and 178 from São Tomé and Príncipe). The following genetic variants were analyzed: intron 4 VNTR in eNOS, rs1050829 in G6PD, -3.7kb α-thalassemic deletion in HBA, rs1800457 in CYB5R3, Hp 1/2 genotype/phenotype in Hp and intron 16 I/D in ACE. Results: Frequencies of genotypes with the 4a allele in eNOS (p<0.001), the G allele in G6PD (p<0.001), the α-3.7 kb in HBA (p <0.001), the C allele in the CYB5R3 (p<0.001) were higher in Peri-equatorial Africa. The Hp 1.1 genotype of Hp has a higher frequency in Peri-equatorial Africa (p=0.002). ACE sho...
Genetic factors of alcoholism influence the phenotypic heterogeneity of alcohol dependence, allow... more Genetic factors of alcoholism influence the phenotypic heterogeneity of alcohol dependence, allowing the higher or lower expression of related aggressive behaviours. The pathogenesis of alcoholism and anti-social behaviour has been connected to serotonergic system dysfunction, given support to examine the association with 44-basepair insertion/deletion polymorphism of serotonin gene transporter (5-HTT). The study aims to assess the relationship between 5-HHTLPR polymorphism, aggressive behaviour and alcohol consumption pattern. There were recruited 97 alcohol dependent patients from the alcoholism unit (Etilo-Risco) of the Psychiatric Service of Santa Maria Hospital. Blood for DNA extraction and clinical and behavioural information was collected during the therapeutic program. Regarding 5-HTTLPR polymorphism prevalence in alcoholic population, 30.7% were homozygotic to l allele, 19.8% were homozygotic to s allele and 49.5% were heterozygotic l/s. Alcoholic patients carrying the l al...
Introdução: A Hipertensão Arterial (HTA) é um fator de risco cardiovascular muito prevalente em P... more Introdução: A Hipertensão Arterial (HTA) é um fator de risco cardiovascular muito prevalente em Portugal. Esta patologia é multifatorial, envolvendo fatores genéticos e ambientais. Objetivo: Este estudo teve como objetivo investigar a potencial implicação de polimorfismos genéticos nos genes eNOS e ECA e da sua interação na suscetibilidade para a HTA na população portuguesa. Métodos: Foi realizado um estudo de caso-controlo para uma amostra de 377 indivíduos portugueses, dos quais 243 hipertensos (90 hipertensos ligeiros e 153 hipertensos graves) e 134 normotensos. As análises polimórficas do VNTR no intrão 4 do gene eNOS e do polimorfismo ECA inserção/deleção (I/D) foram realizadas por reação em cadeia da polimerase (PCR). Resultados: Encontrou-se uma associação entre o alelo 4a do gene eNOS e a hipertensão (p=0,001), sendo mais forte para a hipertensão grave (p<0,001). Em relação ao gene ECA, não se encontraram diferenças estatisticamente significativas entre doentes e controlos. No entanto, ao analisar os 2 polimorfismos em epistasia, encontrou-se uma tendência para associação entre a combinação do alelo 4a do gene eNOS e do alelo D do gene ECA e a hipertensão ligeira (p=0,061). Conclusão: Os nossos resultados evidenciam o contributo do gene eNOS na HTA, assim como da interação epistática entre os genes eNOS e ECA e a suscetibilidade para a hipertensão ligeira na população portuguesa. A identificação de polimorfismos genéticos que possam influenciar o desenvolvimento e gravidade da HTA, bem como as suas interações epistáticas, pode permitir um diagnóstico mais precoce e específico para esta doença tão prevalente em Portugal.
Aguiar L1,2,3, Matos A1,2,3, Gil A1,2,3, Ferreira J1,2,3, Alonso I1,2,3, Rebelo I4,5, Braga L6, A... more Aguiar L1,2,3, Matos A1,2,3, Gil A1,2,3, Ferreira J1,2,3, Alonso I1,2,3, Rebelo I4,5, Braga L6, Almeida S7, Kjollerstrom P6, Faustino P3,8, Bicho M1,2,3, Inácio A1,2,3 1Instituto De Investigação Científica Bento Da Rocha Cabral, Lisboa 2Laboratório de Genética, Faculdade de Medicina da Universidade de Lisboa, Lisboa 3Instituto de Saúde Ambiental, Faculdade de Medicina da Universidade de Lisboa, Lisboa 4Departamento de Bioquímica, Faculdade de Farmácia da Universidade do Porto, Porto 5Instituto de Biologia Molecular e Celular, Porto 6Unidade de Hematologia, Hospital de Dona Estefânia, Lisboa 7Serviço de Genética Médica, Hospital de Dona Estefânia, Lisboa 8Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa
Background. Cardiovascular risk (CVR) underlies aging process and longevity. Previous work points... more Background. Cardiovascular risk (CVR) underlies aging process and longevity. Previous work points to genetic and environmental factors associated with this risk.Objectives. The aim of this research is to look for any CVR gene-gene and gene-multifactorial/lifestyle interactions that may impact health and disease and underlie exceptional longevity.Methods. A case-control study involving 521 both gender individuals, 253 centenarians (100.26±1.98years), and 268 controls (67.51±3.25years), low (LCR,n=107) and high (HCR,n=161) CVR. Hypertension, diabetes, obesity (BMI, kg·m-2), and impaired kidney function were defined according to standard criteria. CVR was calculated using Q risk®. DNA was genotyping (ACE-rs4646994,AGT-rs4762,AGR1-rs5182,GRK4-rs2960306,GRK4-rs1024323,NOS3-rs1799983, andSLC12A3-rs13306673) through iPlex-MassARRAY®, read by MALDI-TOF mass spectrometry, and analyzed by EARTDECODE®.Results. Antilongevity factors consisted (OR 95% CI,p<0.05) BMI 1.558 (1.445-1.680), hyper...
Pulse pressure amplification (PPA) is considered a non-dimensional marker of early vascular agein... more Pulse pressure amplification (PPA) is considered a non-dimensional marker of early vascular ageing, and is inversely and independently associated to future CV events. It is acknowledged that PPA is influenced by heart rate (HR) and its related changes. We aimed at evaluating the effect of ageing on the HR dependence of PPA.
INTRODUÇÃO: A metilenotetrahidrofolato redutase (MTHFR) cataliza a redução irreversível do folato... more INTRODUÇÃO: A metilenotetrahidrofolato redutase (MTHFR) cataliza a redução irreversível do folato que cede grupos metil para a síntese de metionina a partir da homocisteína. São escassos os dados epidemiológicos de distribuição do polimorfismo C677T da MTHFR em diabéticos tipo 2 portugueses com e sem angiopatia. Conhecer a variação polimórfica desta enzima e sua relação com outros factores de risco cardiovascular pode ajudar a definir medidas de prevenção e contribuir para a diminuição de gastos em saúde pública. OBJECTIVO: Avaliar a distribuição do polimorfismo C677T da MTHFR em diabéticos tipo 2 com e sem angiopatia e relacionar com a prevalência de hiperhomocisteinémia e hipercisteinémia. MÉTODOS: Estudo caso-controlo em 134 adultos de ambos os géneros com idades entre 40-75 anos. Foram constituídos dois grupos: I - 69 diabéticos tipo 2 com angiopatia; II - 65 diabéticos tipo 2 sem angiopatia. As concentrações plasmáticas de homocisteína e cisteína foram obtidas por um método de ...
Retinopathy of prematurity (ROP) is a retinal vasoproliferative disorder that represents an impor... more Retinopathy of prematurity (ROP) is a retinal vasoproliferative disorder that represents an important cause of childhood visual impairment and blindness. Although oxidative stress has long been implicated in ROP etiology, other prenatal and perinatal factors are also involved. This review focuses on current research involving inflammation and genetic factors in the pathogenesis of ROP. Increasing evidence suggests that perinatal inflammation or infection contributes to ROP pathogenesis. Cytokines and chemokines with a fundamental role in inflammatory responses and that significantly contributing to angiogenesis are analyzed. Microglia cells, the retinal-resident macrophages, are crucial for retinal homeostasis, however, under sustained pathological stimuli release exaggerated amounts of inflammatory mediators and can promote pathological neovascularization. Current modulation of angiogenic cytokines, such as treatment with antibodies to vascular endothelial growth factor (anti-VEGF), has shown efficacy in the treatment of ocular neovascularization; however, some patients are refractory to anti-VEGF agents, suggesting that other angiogenic or anti-angiogenic cytokines need to be identified. Much evidence suggests that genetic factors contribute to the phenotypic variability of ROP. Several studies have implicated the involvement of candidate genes from different signaling pathways in the development of ROP. However, a genetic component with a major impact on ROP has not yet been discovered. Most studies have limitations and did not replicate results. Future research involving bioinformatics, genomics, and proteomics may contribute to finding more genes associated with ROP and may allow discovering better solutions in the management and treatment of ROP.
There is a clear association between the excessive and cumulative exposure to estrogens and the d... more There is a clear association between the excessive and cumulative exposure to estrogens and the development of cancer in hormone-sensitive tissues, such as the cervix. We studied the association ofCYP1A1 M1(rs4646903) andCOMT(rs4680) polymorphisms in 130 cervical cancer cases (c-cancer) and 179 controls. TheCYP1A1TT genotype was associated with a lower risk for c-cancer (OR = 0.39,p=0.002). The allele C ofCYP1A1was a risk for c-cancer (OR = 2.29,p=0.002). Women withCOMT LLgenotype had a higher risk of developing c-cancer (OR = 4.83,p<0.001). For the interaction of theCYP1A1&COMT, we observed that TC&HL genotypes had a greater risk for c-cancer (OR = 6.07,p=0.006) and TT&HL genotypes had a protection effect (OR = 0.24,p<0.001). TheCYP1A1 TTandCOMT LLgenotypes had higher estradiol levels in c-cancer (p<0.001andp=0.037, resp.). C-cancer is associated with less production of 2-methoxy-estradiol resultant of functional polymorphisms ofCYP1A1andCOMT, separately.CYP1A1andCOMTwork ...
Cervical Cancer - Screening, Treatment and Prevention - Universal Protocols for Ultimate Control, 2018
Current knowledge point to persistence of risk factors for the development of cervical intraepith... more Current knowledge point to persistence of risk factors for the development of cervical intraepithelial neoplasia. The infection with a high-risk oncogenic Human Papillomavirus (HPV) subtypes, most commonly 16 and 18, is a necessary, although not sufficient, condition for development of invasive cervical cancer (ICC) and its precancerous precursor, cervical intra-epithelial neoplasia (CIN). It has been suggested that CIN disease severity and the diversity of vaginal microbiota are associated and this may determine viral persistence and disease behaviour. Our work focuses on the genetic variability associated to the modulation of genotoxicity induced by vaginal microbiota diversity. Relatively little is known about the mechanisms associated with clearance or persistence of HPV infection, therefore we hypothesized that may be under the influence of the genetic background.
The gene TAS2R38 single nucleotide polymorphisms (SNPs-P49A, A262V and V296I) can condition bitte... more The gene TAS2R38 single nucleotide polymorphisms (SNPs-P49A, A262V and V296I) can condition bitter tasting by PAV (proline–alanine–valine) and non-bitter-tasting by AVI (alanine–valine–isoleucine) homozygosity. We evaluated this polymorphisms association with thyroid function, metabolism and anthropometry parameters determined by: Endpoint analysis (SNPs); DXA (fat mass-%, total fat mass—kg, lean mass—kg); Standard methods (lipid metabolism parameters, HbA1c-%, glycemia—mg/dL, insulinemia—µIU/mL, HOMA-IR, uricemia—mg/dL, calcemia—mg/dL and BMI—kg/m2); ELISA (leptinemia—ng/mL); Spectrophotometry (Angiotensin Converting Enzyme activity—UI/L). Statistics: SPSS program; OR [IC95%]; p < 0.05. Sample: 114 hypothyroid, 49 hyperthyroid, and 179 controls. An association between A262V-valine–valine and hypothyroidism/hyperthyroidism was verified (OR = 2.841; IC95% [1.726–4.676]), p < 0.001/OR = 8.915; IC95% [4.286–18.543]), p < 0.001). Protector effect from thyroid dysfunction: A262V...
Psoriasis is a multifactorial disease, with many genetic risk factors, one of which seems to be t... more Psoriasis is a multifactorial disease, with many genetic risk factors, one of which seems to be the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism. ACE activity has been shown to be higher in psoriatic patients and it suggests an oxidative stress state, as seen in many cardiovascular disorders. We aimed to explore the association between ACE activity and polymorphisms and cardiovascular risk amongst psoriatic patients. We included 64 psoriatic patients and 1091 controls and compared ACE I/D polymorphism genotype and serum activity for both groups. ACE genotypes were similar in psoriatic patients and controls. Notably, serum ACE activity was higher in psoriatic patients (19.09 ± 2.86 U/mL) compared to controls (11.85 ± 0.40 U/mL), p = 0.015. Non-HDL cholesterol was significantly lower in II polymorphism (p = 0.037). Psoriatic activity (PASI) was associated with a higher cardiovascular risk estimated by lower HDL concentrations (r = −0.496, p = 0.007), and h...
The two antagonistic systems of angiotensin converting enzyme (ACE)-1 and ACE-2 are in the “eye o... more The two antagonistic systems of angiotensin converting enzyme (ACE)-1 and ACE-2 are in the “eye of the hurricane” of severe acute respiratory syndrome coronavirus (SARS-CoV-2). The receptor of the SARS-CoV-2 is the same as ACE-2, which causes its under-expression after binding it, followed by the internalization of the complex virus-ACE-2. ACE-2 have multiple functions with specially relevance in cardiovascular diseases. Furthermore, the non-enzymatic role of ACE-2 gives rise to a Hartnup disease, a phenocopy involving microbiota. With this chapter, we intent to explore the key pathways involved in SARS-CoV-2 infection, from the host perspective, considering our hypothesis related to transporter of neutral amino acids, which includes tryptophan precursor of serotonin and kynurenine.
Abstract Hypertension is a multifactorial condition of genetic and environmental nature. In Portu... more Abstract Hypertension is a multifactorial condition of genetic and environmental nature. In Portugal the mean prevalence of hypertension in the population is 45.5%. The aim of this study is to evaluate the contribution of anthropometric, physiological and genetic factors (eNOS and ACE) to the development of hypertension in a Portuguese population. A case-control study was conducted in a sample of 377 individuals, 243 hypertensives and 134 normotensives. The polymorphic analyses of intron 4 VNTR in the eNOS gene and the insertion/deletion (I/D) in ACE gene were performed by polymerase chain reaction (PCR). Higher body mass index (BMI) values, higher glycemia and HOMA -IR levels and the 4a allele of the eNOS gene were associated with hypertension. Among the hypertensive group, the allele 4a (eNOS) was associated with higher levels of HbA1c, and the D allele (ACE) with higher glycemia and HOMA-IR levels. Our results highlight the contribution of eNOS and ACE genes as important players for development of hypertension in the Portuguese population. We believe that a combinatory clinical approach including the traditional anthropomorphic and physiological parameters together with target specific genetic analysis, can be more elucidative in establishing a susceptibility profile on multifactorial conditions as hypertension.
Obesity among children has emerged as a serious public health problem. The growing prevalence of ... more Obesity among children has emerged as a serious public health problem. The growing prevalence of childhood obesity has led to the appearance of serious complications, including a chronic systemic inflammation associated with oxidative stress. In the present study, we analysed the interaction between two genes related with iron metabolism - HFE and haptoglobin – and the plasmatic concentration of glutathione, as a way to evaluate the antioxidant response capacity in obesity. To achieve this, 118 obese children and 89 eutrophic children were recruited for the study. Results showed that although obese children present a significantly decreased tGSH levels, once we analysed separately children based on their haptoglobin phenotype, the decreased tGSH levels is significant only for the Hp 2 allele. Additionally, Hp 2.2 obese children carrying H63D polymorphism show significantly lower tGSH/GSSG values. Our results found an association of haptoglobin and HFE with oxidative stress in child...
BACKGROUND: Sickle cell anemia (SCA) is an inherited blood disorder. SCA patients present clinica... more BACKGROUND: Sickle cell anemia (SCA) is an inherited blood disorder. SCA patients present clinical and hematologic variability that cannot be only explained by the single mutation in the beta-globin gene. Others genetic modifiers and environmental effects are important for the clinical phenotype. SCA patients present arginine deficiency that contributes to a lower nitric oxide (NO) bioactivity. OBJECTIVE: The aim of this work is to determine the association between hematological and biochemical parameters and genetic variants from eNOS gene, in pediatric SCA patients. METHODS: 26 pediatric SCA patients were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques in three important eNOS gene polymorphisms-rs2070744, rs1799983 and intron 4 VNTR. RESULTS: Results from this study show a significant statistical association between some parameters and genetic variants: an increased reticulocyte count and high serum lactate dehydrogenase levels were associated with both the rs2070744 TT and the rs1799983 GG genotypes at eNOS gene and high levels of neutrophils were associated with the eNOS4a allele at intron 4 VNTR. CONCLUSIONS: Our results reinforce the importance of NO bioactivity in SCA. We presume that NO, and its precursors might be used as therapy to improve the quality of life of SCA patients.
Objectivo: Verificar a associacao entre o fenotipo da haptoglobina (Hp), uma proteina de fase agu... more Objectivo: Verificar a associacao entre o fenotipo da haptoglobina (Hp), uma proteina de fase aguda, e a concentracao plasmatica de glutationo total (GSHt) em adolescentes obesos, como forma de avaliar a capacidade antioxidante de resposta ao processo inflamatorio relacionado com a obesidade. Amostra Populacional. Foram estudados 69 adolescentes obesos, de acordo com o valor de corte de Cole, com media de idades de 11,2 ± 1,17 anos e IMC 27,4 ± 4,8. O grupo controlo e constituido por 104 adolescentes eutroficos. Metodos : A determinacao do fenotipo da haptoglobina plasmatica foi efectuada por electroforese em gel de poliacrilamida e a concentracao de GSHt foi obtida por espectrofluorimetria, usando o o-ftaldeido (OPT) como fluoroforo. Resultados: Verificou-se que a concentracao de GSHt nos adolescentes obesos e significativamente inferior a dos adolescentes do grupo controlo (mediana: 34,65 vs 48,90 μmol/L; p<0,001), estando a razao entre o GSHt e a forma oxidada do glu tationo (...
Revista Portuguesa de Endocrinologia, Diabetes e Metabolismo, 2016
The aim is to study the frequency of vertebral pain syndrome in men and women of older age groups... more The aim is to study the frequency of vertebral pain syndrome in men and women of older age groups depending on the bone mineral density (BMD). Methods: We have examined 1,934 people aged 50-89 years, among them 1697 women and 237 men. The frequency of back pain syndrome was studied depending on BMD (osteoporosis, osteopenia, and norm). BMD at all sites was measured by DXA using a Prodigy densitometer (GE). Results: The frequency of pain syndrome among older age groups is significantly higher in women compared with men (88.3% (1,499/1,697) vs 84.8% (201/237), accordingly, p = 0.01). In women of 50-89 years, with osteoporosis and no fractures in their anamnesis, pain syndrome in the thoracic and lumbar spine is significantly higher in comparison with women who have osteopenia (p = 0.01) and normal BMD (p = 0.02) and compared to men with a similar BMD state (osteoporosis; (91.8% (337/367) vs 76.2% (16/21), accordingly, p = 0.01)). The frequency of pain syndrome in the thoracic and the lumbar spine in women is associated with BMD. The presence of osteoporosis increases the risk of pain syndrome in the thoracic spine (RR = 1.27, 95%CI: 1.12-1.44, p = 0.0001). In older women, the presence of low-energy fractures significantly impacts the increasing frequency of pain in the thoracic region regardless of the BMD state. Conclusions: The frequency of pain among older age groups is significantly higher in women compared with men. In women of older age groups, the presence of low-energy fractures significantly increases the frequency of pain in the thoracic region, regardless of the state of BMD. In women 50-89 years old, with osteoporosis and no low-energy fractures, the frequency of pain in the thoracic and lumbar regions is significantly higher compared to women with osteopenia and normal BMD, as well as compared to men with a similar BMD state (osteoporosis).
Background: Since the emergence of the genus Homo, hominids have occupied a wide variety of envir... more Background: Since the emergence of the genus Homo, hominids have occupied a wide variety of environments, facing different selective pressures. Objectives: The aim this study is to compare genotype frequencies between South-West Europe and Peri-equatorial Africa in genes potentially modulators of blood pressure. Methods: The analyzed sample consisted of 325 individuals from Portugal and 226 individuals from Africa (48 from Mozambique and 178 from São Tomé and Príncipe). The following genetic variants were analyzed: intron 4 VNTR in eNOS, rs1050829 in G6PD, -3.7kb α-thalassemic deletion in HBA, rs1800457 in CYB5R3, Hp 1/2 genotype/phenotype in Hp and intron 16 I/D in ACE. Results: Frequencies of genotypes with the 4a allele in eNOS (p<0.001), the G allele in G6PD (p<0.001), the α-3.7 kb in HBA (p <0.001), the C allele in the CYB5R3 (p<0.001) were higher in Peri-equatorial Africa. The Hp 1.1 genotype of Hp has a higher frequency in Peri-equatorial Africa (p=0.002). ACE sho...
Genetic factors of alcoholism influence the phenotypic heterogeneity of alcohol dependence, allow... more Genetic factors of alcoholism influence the phenotypic heterogeneity of alcohol dependence, allowing the higher or lower expression of related aggressive behaviours. The pathogenesis of alcoholism and anti-social behaviour has been connected to serotonergic system dysfunction, given support to examine the association with 44-basepair insertion/deletion polymorphism of serotonin gene transporter (5-HTT). The study aims to assess the relationship between 5-HHTLPR polymorphism, aggressive behaviour and alcohol consumption pattern. There were recruited 97 alcohol dependent patients from the alcoholism unit (Etilo-Risco) of the Psychiatric Service of Santa Maria Hospital. Blood for DNA extraction and clinical and behavioural information was collected during the therapeutic program. Regarding 5-HTTLPR polymorphism prevalence in alcoholic population, 30.7% were homozygotic to l allele, 19.8% were homozygotic to s allele and 49.5% were heterozygotic l/s. Alcoholic patients carrying the l al...
Introdução: A Hipertensão Arterial (HTA) é um fator de risco cardiovascular muito prevalente em P... more Introdução: A Hipertensão Arterial (HTA) é um fator de risco cardiovascular muito prevalente em Portugal. Esta patologia é multifatorial, envolvendo fatores genéticos e ambientais. Objetivo: Este estudo teve como objetivo investigar a potencial implicação de polimorfismos genéticos nos genes eNOS e ECA e da sua interação na suscetibilidade para a HTA na população portuguesa. Métodos: Foi realizado um estudo de caso-controlo para uma amostra de 377 indivíduos portugueses, dos quais 243 hipertensos (90 hipertensos ligeiros e 153 hipertensos graves) e 134 normotensos. As análises polimórficas do VNTR no intrão 4 do gene eNOS e do polimorfismo ECA inserção/deleção (I/D) foram realizadas por reação em cadeia da polimerase (PCR). Resultados: Encontrou-se uma associação entre o alelo 4a do gene eNOS e a hipertensão (p=0,001), sendo mais forte para a hipertensão grave (p<0,001). Em relação ao gene ECA, não se encontraram diferenças estatisticamente significativas entre doentes e controlos. No entanto, ao analisar os 2 polimorfismos em epistasia, encontrou-se uma tendência para associação entre a combinação do alelo 4a do gene eNOS e do alelo D do gene ECA e a hipertensão ligeira (p=0,061). Conclusão: Os nossos resultados evidenciam o contributo do gene eNOS na HTA, assim como da interação epistática entre os genes eNOS e ECA e a suscetibilidade para a hipertensão ligeira na população portuguesa. A identificação de polimorfismos genéticos que possam influenciar o desenvolvimento e gravidade da HTA, bem como as suas interações epistáticas, pode permitir um diagnóstico mais precoce e específico para esta doença tão prevalente em Portugal.
Aguiar L1,2,3, Matos A1,2,3, Gil A1,2,3, Ferreira J1,2,3, Alonso I1,2,3, Rebelo I4,5, Braga L6, A... more Aguiar L1,2,3, Matos A1,2,3, Gil A1,2,3, Ferreira J1,2,3, Alonso I1,2,3, Rebelo I4,5, Braga L6, Almeida S7, Kjollerstrom P6, Faustino P3,8, Bicho M1,2,3, Inácio A1,2,3 1Instituto De Investigação Científica Bento Da Rocha Cabral, Lisboa 2Laboratório de Genética, Faculdade de Medicina da Universidade de Lisboa, Lisboa 3Instituto de Saúde Ambiental, Faculdade de Medicina da Universidade de Lisboa, Lisboa 4Departamento de Bioquímica, Faculdade de Farmácia da Universidade do Porto, Porto 5Instituto de Biologia Molecular e Celular, Porto 6Unidade de Hematologia, Hospital de Dona Estefânia, Lisboa 7Serviço de Genética Médica, Hospital de Dona Estefânia, Lisboa 8Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa
Background. Cardiovascular risk (CVR) underlies aging process and longevity. Previous work points... more Background. Cardiovascular risk (CVR) underlies aging process and longevity. Previous work points to genetic and environmental factors associated with this risk.Objectives. The aim of this research is to look for any CVR gene-gene and gene-multifactorial/lifestyle interactions that may impact health and disease and underlie exceptional longevity.Methods. A case-control study involving 521 both gender individuals, 253 centenarians (100.26±1.98years), and 268 controls (67.51±3.25years), low (LCR,n=107) and high (HCR,n=161) CVR. Hypertension, diabetes, obesity (BMI, kg·m-2), and impaired kidney function were defined according to standard criteria. CVR was calculated using Q risk®. DNA was genotyping (ACE-rs4646994,AGT-rs4762,AGR1-rs5182,GRK4-rs2960306,GRK4-rs1024323,NOS3-rs1799983, andSLC12A3-rs13306673) through iPlex-MassARRAY®, read by MALDI-TOF mass spectrometry, and analyzed by EARTDECODE®.Results. Antilongevity factors consisted (OR 95% CI,p<0.05) BMI 1.558 (1.445-1.680), hyper...
Pulse pressure amplification (PPA) is considered a non-dimensional marker of early vascular agein... more Pulse pressure amplification (PPA) is considered a non-dimensional marker of early vascular ageing, and is inversely and independently associated to future CV events. It is acknowledged that PPA is influenced by heart rate (HR) and its related changes. We aimed at evaluating the effect of ageing on the HR dependence of PPA.
INTRODUÇÃO: A metilenotetrahidrofolato redutase (MTHFR) cataliza a redução irreversível do folato... more INTRODUÇÃO: A metilenotetrahidrofolato redutase (MTHFR) cataliza a redução irreversível do folato que cede grupos metil para a síntese de metionina a partir da homocisteína. São escassos os dados epidemiológicos de distribuição do polimorfismo C677T da MTHFR em diabéticos tipo 2 portugueses com e sem angiopatia. Conhecer a variação polimórfica desta enzima e sua relação com outros factores de risco cardiovascular pode ajudar a definir medidas de prevenção e contribuir para a diminuição de gastos em saúde pública. OBJECTIVO: Avaliar a distribuição do polimorfismo C677T da MTHFR em diabéticos tipo 2 com e sem angiopatia e relacionar com a prevalência de hiperhomocisteinémia e hipercisteinémia. MÉTODOS: Estudo caso-controlo em 134 adultos de ambos os géneros com idades entre 40-75 anos. Foram constituídos dois grupos: I - 69 diabéticos tipo 2 com angiopatia; II - 65 diabéticos tipo 2 sem angiopatia. As concentrações plasmáticas de homocisteína e cisteína foram obtidas por um método de ...
Retinopathy of prematurity (ROP) is a retinal vasoproliferative disorder that represents an impor... more Retinopathy of prematurity (ROP) is a retinal vasoproliferative disorder that represents an important cause of childhood visual impairment and blindness. Although oxidative stress has long been implicated in ROP etiology, other prenatal and perinatal factors are also involved. This review focuses on current research involving inflammation and genetic factors in the pathogenesis of ROP. Increasing evidence suggests that perinatal inflammation or infection contributes to ROP pathogenesis. Cytokines and chemokines with a fundamental role in inflammatory responses and that significantly contributing to angiogenesis are analyzed. Microglia cells, the retinal-resident macrophages, are crucial for retinal homeostasis, however, under sustained pathological stimuli release exaggerated amounts of inflammatory mediators and can promote pathological neovascularization. Current modulation of angiogenic cytokines, such as treatment with antibodies to vascular endothelial growth factor (anti-VEGF), has shown efficacy in the treatment of ocular neovascularization; however, some patients are refractory to anti-VEGF agents, suggesting that other angiogenic or anti-angiogenic cytokines need to be identified. Much evidence suggests that genetic factors contribute to the phenotypic variability of ROP. Several studies have implicated the involvement of candidate genes from different signaling pathways in the development of ROP. However, a genetic component with a major impact on ROP has not yet been discovered. Most studies have limitations and did not replicate results. Future research involving bioinformatics, genomics, and proteomics may contribute to finding more genes associated with ROP and may allow discovering better solutions in the management and treatment of ROP.
There is a clear association between the excessive and cumulative exposure to estrogens and the d... more There is a clear association between the excessive and cumulative exposure to estrogens and the development of cancer in hormone-sensitive tissues, such as the cervix. We studied the association ofCYP1A1 M1(rs4646903) andCOMT(rs4680) polymorphisms in 130 cervical cancer cases (c-cancer) and 179 controls. TheCYP1A1TT genotype was associated with a lower risk for c-cancer (OR = 0.39,p=0.002). The allele C ofCYP1A1was a risk for c-cancer (OR = 2.29,p=0.002). Women withCOMT LLgenotype had a higher risk of developing c-cancer (OR = 4.83,p<0.001). For the interaction of theCYP1A1&COMT, we observed that TC&HL genotypes had a greater risk for c-cancer (OR = 6.07,p=0.006) and TT&HL genotypes had a protection effect (OR = 0.24,p<0.001). TheCYP1A1 TTandCOMT LLgenotypes had higher estradiol levels in c-cancer (p<0.001andp=0.037, resp.). C-cancer is associated with less production of 2-methoxy-estradiol resultant of functional polymorphisms ofCYP1A1andCOMT, separately.CYP1A1andCOMTwork ...
Cervical Cancer - Screening, Treatment and Prevention - Universal Protocols for Ultimate Control, 2018
Current knowledge point to persistence of risk factors for the development of cervical intraepith... more Current knowledge point to persistence of risk factors for the development of cervical intraepithelial neoplasia. The infection with a high-risk oncogenic Human Papillomavirus (HPV) subtypes, most commonly 16 and 18, is a necessary, although not sufficient, condition for development of invasive cervical cancer (ICC) and its precancerous precursor, cervical intra-epithelial neoplasia (CIN). It has been suggested that CIN disease severity and the diversity of vaginal microbiota are associated and this may determine viral persistence and disease behaviour. Our work focuses on the genetic variability associated to the modulation of genotoxicity induced by vaginal microbiota diversity. Relatively little is known about the mechanisms associated with clearance or persistence of HPV infection, therefore we hypothesized that may be under the influence of the genetic background.
The gene TAS2R38 single nucleotide polymorphisms (SNPs-P49A, A262V and V296I) can condition bitte... more The gene TAS2R38 single nucleotide polymorphisms (SNPs-P49A, A262V and V296I) can condition bitter tasting by PAV (proline–alanine–valine) and non-bitter-tasting by AVI (alanine–valine–isoleucine) homozygosity. We evaluated this polymorphisms association with thyroid function, metabolism and anthropometry parameters determined by: Endpoint analysis (SNPs); DXA (fat mass-%, total fat mass—kg, lean mass—kg); Standard methods (lipid metabolism parameters, HbA1c-%, glycemia—mg/dL, insulinemia—µIU/mL, HOMA-IR, uricemia—mg/dL, calcemia—mg/dL and BMI—kg/m2); ELISA (leptinemia—ng/mL); Spectrophotometry (Angiotensin Converting Enzyme activity—UI/L). Statistics: SPSS program; OR [IC95%]; p < 0.05. Sample: 114 hypothyroid, 49 hyperthyroid, and 179 controls. An association between A262V-valine–valine and hypothyroidism/hyperthyroidism was verified (OR = 2.841; IC95% [1.726–4.676]), p < 0.001/OR = 8.915; IC95% [4.286–18.543]), p < 0.001). Protector effect from thyroid dysfunction: A262V...
Psoriasis is a multifactorial disease, with many genetic risk factors, one of which seems to be t... more Psoriasis is a multifactorial disease, with many genetic risk factors, one of which seems to be the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism. ACE activity has been shown to be higher in psoriatic patients and it suggests an oxidative stress state, as seen in many cardiovascular disorders. We aimed to explore the association between ACE activity and polymorphisms and cardiovascular risk amongst psoriatic patients. We included 64 psoriatic patients and 1091 controls and compared ACE I/D polymorphism genotype and serum activity for both groups. ACE genotypes were similar in psoriatic patients and controls. Notably, serum ACE activity was higher in psoriatic patients (19.09 ± 2.86 U/mL) compared to controls (11.85 ± 0.40 U/mL), p = 0.015. Non-HDL cholesterol was significantly lower in II polymorphism (p = 0.037). Psoriatic activity (PASI) was associated with a higher cardiovascular risk estimated by lower HDL concentrations (r = −0.496, p = 0.007), and h...
The two antagonistic systems of angiotensin converting enzyme (ACE)-1 and ACE-2 are in the “eye o... more The two antagonistic systems of angiotensin converting enzyme (ACE)-1 and ACE-2 are in the “eye of the hurricane” of severe acute respiratory syndrome coronavirus (SARS-CoV-2). The receptor of the SARS-CoV-2 is the same as ACE-2, which causes its under-expression after binding it, followed by the internalization of the complex virus-ACE-2. ACE-2 have multiple functions with specially relevance in cardiovascular diseases. Furthermore, the non-enzymatic role of ACE-2 gives rise to a Hartnup disease, a phenocopy involving microbiota. With this chapter, we intent to explore the key pathways involved in SARS-CoV-2 infection, from the host perspective, considering our hypothesis related to transporter of neutral amino acids, which includes tryptophan precursor of serotonin and kynurenine.
Abstract Hypertension is a multifactorial condition of genetic and environmental nature. In Portu... more Abstract Hypertension is a multifactorial condition of genetic and environmental nature. In Portugal the mean prevalence of hypertension in the population is 45.5%. The aim of this study is to evaluate the contribution of anthropometric, physiological and genetic factors (eNOS and ACE) to the development of hypertension in a Portuguese population. A case-control study was conducted in a sample of 377 individuals, 243 hypertensives and 134 normotensives. The polymorphic analyses of intron 4 VNTR in the eNOS gene and the insertion/deletion (I/D) in ACE gene were performed by polymerase chain reaction (PCR). Higher body mass index (BMI) values, higher glycemia and HOMA -IR levels and the 4a allele of the eNOS gene were associated with hypertension. Among the hypertensive group, the allele 4a (eNOS) was associated with higher levels of HbA1c, and the D allele (ACE) with higher glycemia and HOMA-IR levels. Our results highlight the contribution of eNOS and ACE genes as important players for development of hypertension in the Portuguese population. We believe that a combinatory clinical approach including the traditional anthropomorphic and physiological parameters together with target specific genetic analysis, can be more elucidative in establishing a susceptibility profile on multifactorial conditions as hypertension.
Obesity among children has emerged as a serious public health problem. The growing prevalence of ... more Obesity among children has emerged as a serious public health problem. The growing prevalence of childhood obesity has led to the appearance of serious complications, including a chronic systemic inflammation associated with oxidative stress. In the present study, we analysed the interaction between two genes related with iron metabolism - HFE and haptoglobin – and the plasmatic concentration of glutathione, as a way to evaluate the antioxidant response capacity in obesity. To achieve this, 118 obese children and 89 eutrophic children were recruited for the study. Results showed that although obese children present a significantly decreased tGSH levels, once we analysed separately children based on their haptoglobin phenotype, the decreased tGSH levels is significant only for the Hp 2 allele. Additionally, Hp 2.2 obese children carrying H63D polymorphism show significantly lower tGSH/GSSG values. Our results found an association of haptoglobin and HFE with oxidative stress in child...
BACKGROUND: Sickle cell anemia (SCA) is an inherited blood disorder. SCA patients present clinica... more BACKGROUND: Sickle cell anemia (SCA) is an inherited blood disorder. SCA patients present clinical and hematologic variability that cannot be only explained by the single mutation in the beta-globin gene. Others genetic modifiers and environmental effects are important for the clinical phenotype. SCA patients present arginine deficiency that contributes to a lower nitric oxide (NO) bioactivity. OBJECTIVE: The aim of this work is to determine the association between hematological and biochemical parameters and genetic variants from eNOS gene, in pediatric SCA patients. METHODS: 26 pediatric SCA patients were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques in three important eNOS gene polymorphisms-rs2070744, rs1799983 and intron 4 VNTR. RESULTS: Results from this study show a significant statistical association between some parameters and genetic variants: an increased reticulocyte count and high serum lactate dehydrogenase levels were associated with both the rs2070744 TT and the rs1799983 GG genotypes at eNOS gene and high levels of neutrophils were associated with the eNOS4a allele at intron 4 VNTR. CONCLUSIONS: Our results reinforce the importance of NO bioactivity in SCA. We presume that NO, and its precursors might be used as therapy to improve the quality of life of SCA patients.
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Papers by Manuel Bicho