Medical principles and practice : international journal of the Kuwait University, Health Science Centre, 2017
To examine the concordance between lifestyle practices and beliefs of people living in Kuwait, an... more To examine the concordance between lifestyle practices and beliefs of people living in Kuwait, and between their lifestyle practices and established evidence-informed recommendations for health. A cross-sectional interview questionnaire study was conducted using a convenience sample of 100 adults living in Kuwait (age range 19-75 years). The interview included sections on demographics, and lifestyle-related practices and beliefs related to smoking, diet/nutrition, physical activity/exercise, sleep, and stress. Diet/nutrition and physical activity/exercise benchmarks were based on international standards. Analyses included descriptive statistics and the χ2 test. Beliefs about the importance of nutrition in lifestyle-related conditions were limited, and this was apparent in participants' dietary habits, e.g., low consumption of fruit/vegetables and multigrains: 16 (16%) and 9 (9%) met the recommended guidelines, respectively. Ninety-nine (99%) believed physical activity/exercise a...
The expression of interferon inducible genes are reported to be heightened in systemic lupus eryt... more The expression of interferon inducible genes are reported to be heightened in systemic lupus erythematosus (SLE); nevertheless, not much is known regarding the genetic variants underlying these genes and their role in the pathogenesis of disease. Herein, we aim to explore the potential association and contribution of polymorphisms in MX1 gene (i) promoter with part of exon 1 (ii) intron 6, and (iii) their resulting haplotypes, with susceptibility to SLE. A total of 306 subjects, 152 SLE and 154 healthy controls (HC), were screened by direct sequencing method. Statistical analysis was carried out using appropriate software. The screening region of interest in MX1 revealed the existence of promoter (−123C/A, −88G/T, −20 A/C) and intron 6 (+9862G/A, +10190G/A, +9901C/G, +9920C/A, +9959C/T, +10047A/G) variants in SLE and HC. A significant association was observed between MX1 −88G/T SNP and susceptibility to SLE (χ2 = 4.18, p = 0.04, OR = 1.89, 95 % CI 1.03–3.5). Haplotype analysis also revealed increased risk of SLE among individuals carrying CTA haplotype (−123 C, −88 T, −20 A) (χ2 = 5.74, p = 0.017, OR = 4.28, 95 % CI 1.30–14.06). None of the other tested variants showed any significant association with SLE. The present study is the first to reveal the influence of genetic variation in MX1 gene in susceptibility to SLE.
Abstract Introduction Autoimmunity is one of the top ten causes of morbidity and mortality in fem... more Abstract Introduction Autoimmunity is one of the top ten causes of morbidity and mortality in female children and young to middle aged woman, with similar prevalence rate across different geographic areas. About 5-30% of autoimmune patients are inclined to develop additional autoimmune diseases leading to the development of overlap diseases. An overlap between Lupus and Rheumatoid Arthritis (RA) referred to as Rhupus has been much on debate, whether it represents a single distinct entity or an overlap disease? Herein we reviewed the literature over the past 54 years to characterise rhupus subjects and to support the theory of overlap. Discussion Rhupus is known to be a complex musculoskeletal autoimmune disease defined by erosive polyarthritis. The exact cause and triggers of rhupus remains unknown with limited studies suggesting the combined role of genetic, immunological, hormonal and environmental factors in the progression of disease. Among genetic factors, HLA-DR alleles were s...
The global emergence of drug-resistant malarial parasites necessitates identification and charact... more The global emergence of drug-resistant malarial parasites necessitates identification and characterization of novel drug targets. Three reactions are involved in methylenetetrahydrofolate recycling: Thymidylate synthase (TS), dihydrofolate reductase (DHFR), and serine hydroxymethyltransferase (SHMT). Malarial bifunctional DHFR-TS is a well-studied, important target of established drugs such as pyrimethamine and cycloguanil. In sharp contrast, malarial SHMT remains largely uncharacterized. In the present study, a Plasmodium falciparum SHMT coding region was characterized. It had 1603 bp including two introns near the 5'-end of the gene: one 118 bp intron immediately after the start methionine and a 159 bp intron after an additional 34 amino acids. The three exons together coded for a 442 amino acid protein with 38-47% identity to SHMT sequences from other species. Expression of malarial SHMT coding sequence (minus the introns) into glyA mutants of Escherichia coli relieved glycine auxotrophy and permitted direct assay of SHMT catalytic activity in bacterial cell lysates. This is the first SHMT cloned and expressed from a protozoan parasite. The molecular tools developed in this study will be useful for developing potential antimalarials directed at SHMT.
Objectives: We aimed to investigate germline mutation in another extended von Hippel-Lindau (VHL)... more Objectives: We aimed to investigate germline mutation in another extended von Hippel-Lindau (VHL) family in Kuwait with Arabian and Persian genetic admixture. Materials andMethod: Polymerase chain reaction (PCR) followed by single-strand conformation polymorphism (SSCP) and direct sequencing of the PCR amplicons, that showed clear band shift, were used to screen the VHL gene in the index patient, 20 members of her family and 55 healthy controls of matching ethnicity. Result: The clinical history of all patients revealed multiple hemangioblastomas in various organs without pheochromocytomas. SSCP showed a clear band shift in 2 PCR amplicons, which were then sequenced. One was in the promoter region revealing a polymorphic site (A–123G) found as heterozygous in 40% of the healthy control subjects of the same ethnicity. The second band shift was in exon 2 seen in all clinically diagnosed VHL cases but not in the healthy members of the family or the screened healthy population. Direct s...
Objective: The objective of the present study was to determine whether saponin hemolysis could im... more Objective: The objective of the present study was to determine whether saponin hemolysis could improve microscopic detection of malaria parasites in human blood, since it has been previously reported that the technique has been used to enrich Plasmodium falciparum culture to ≧90% parasitemia. Material and Methods: Blood samples from suspected malaria cases were first examined in routine thick and thin smears under the microscope. The sample (1 ml) was then hemolyzed with 0.015% saponin in saline and centrifuged, the separated pellet was stained with Giemsa stain and examined microscopically, using PCR to confirm species identification. Results: With P. falciparum in vitro culture, the proportions of infected erythrocytes were approximately 0.7–2% before and 65–97% after saponin hemolysis, confirming published reports. In contrast, there was little or no increase in the proportions of intact infected erythrocytes after saponin hemolysis of clinical blood specimens. However, 20–600 he...
Objective: This study was undertaken to determine the prevalence of congenital cytomegalovirus (C... more Objective: This study was undertaken to determine the prevalence of congenital cytomegalovirus (CMV) infection in pregnant women at the end of pregnancy in Kuwait using cord blood and maternal urine. Subjects and Methods: Urine samples were collected prior to childbirth, and cord blood was collected immediately after delivery from 983 women. Anti-CMV IgG and IgM antibodies were determined using ELISA; CMV DNA was detected using nested PCR, and viral load was calculated using real-time PCR. CMV concentration in samples was categorized as low when the viral load ≤103 copies/µl, intermediate when the viral load = 103–104 copies/µl, and high when the viral load >104 copies/µl. The cord blood serology outcome was compared to cord blood PCR, cord blood viral load, maternal urine PCR and viral load analyses. Results: Serology showed that of the 983 cord blood samples, 89 (9%) were positive for anti-CMV IgM antibodies; PCR test showed 44 (4.5%) contained CMV DNA, and there was a high vir...
International Journal of Laboratory Hematology, 2010
SummaryHomozygous β‐thalassemia is a common genetic disorder in the Arabian Peninsula and an impo... more SummaryHomozygous β‐thalassemia is a common genetic disorder in the Arabian Peninsula and an important cause of morbidity in Kuwait. The anemia is so severe that chronic blood transfusions, and the resulting iron overload, cause a shift in immunoregulatory balances and a deficiency in zinc. It was reported that individual immunological profile of CD8+ T‐lymphocytes may have a modifying effect on the severity of iron overload in HFE homozygous hemochromatosis patients, with low numbers being negatively correlated with the total amount of body iron stores. This has not been tested in thalassemia major patients. This study was designed to utilize flow cytometric immunophenotyping to characterize effects of regular blood transfusion, and high serum ferritin levels because of irregular use of iron chelation therapy on T lymphocytes (CD2, CD3, CD4 and CD8), B lymphocytes (CD19) and natural killer cells (CD56) and zinc levels in the blood of patients with thalassemia major (n = 49) and hea...
SummaryDeoxyribonuclease I (DNASE1) may be responsible for the removal of DNA from nuclear antige... more SummaryDeoxyribonuclease I (DNASE1) may be responsible for the removal of DNA from nuclear antigens at sites of high cell turnover, thus preventing the onset of systemic lupus erythematosus (SLE). The purpose of this study was to screen DNASE1 gene for mutations that may have an effect on susceptibility to develop SLE. DNA was extracted from 76 Kuwaiti SLE patients and 92 race‐matched controls. PCR‐direct sequencing was used to screen DNASE1 promoter, coding sequence and exon–intron boundaries for mutation. Association of genomic variations was assessed using a Chi‐square test. Molecular analysis of the DNASE1 gene did not reveal any mutation. However, a 56‐bp repeat was detected in intron4 which was previously reported and named HumDN1. The allelic and genotypic distributions of the HumDN1 VNTR were compared between SLE patients and healthy subjects. Alleles were denoted as 2, 3, 4, 5 and 6 corresponding to the number of repeats of the 56 bp unit. Alleles 4, 5, and 6 showed signifi...
ABSTRACT Members of arrestin/beta-arrestin protein family are thought to participate in agonist-m... more ABSTRACT Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors, including rhodopsin and beta2-adrenergic receptor. Unlike in human and cow, splice variants of this protein family in rat have not been studied extensively, and there has been no report on their existence at protein level. Hence, a previous report by others on the localization of both beta-arrestin-1 and -2 in a wide range of innervated rat tissues could imply their broad receptor specificity. In this report we show the presence of two alternatively spliced forms of beta-arrestin-1 in several rat tissues using both reverse transcription-polymerase chain reaction and Western immunoblot. Splicing of beta-arrestin-1 pre-mRNA appears to be subject to differential regulation between the rat CNS and peripheral tissues. In contrast, we detected no splice variants of beta-arrestin-2 in rat. A comparison of the genomic DNA sequences of bovine and rat beta-arrestin-2, where the splicing of bovine beta-arrestin-2 mRNA has been reported, revealed a high degree of homology in their organization of exons and introns as well as certain differences that might be responsible for the different processing of beta-arrestin-2 mRNA in the two species. Our two-dimensional isoelectric focusing gels using rat spinal cord and heart tissues demonstrate isoelectric heterogeneity of rat beta-arrestin-1, suggesting that beta-arrestin-1 is subject to post-translational modification unlike beta-arrestin-2.
Analysing two CTLA-4 markers [exon 1 A49G single nucleotide polymorphism (SNP) and exon 4 3&a... more Analysing two CTLA-4 markers [exon 1 A49G single nucleotide polymorphism (SNP) and exon 4 3'UTR (AT)n repeat] and the ICOS intron 4 (GT)n marker for their potential association with HT, and exploring the effect of the tested SNPs on the CTLA-4 isoform expression at the mRNA and protein levels. Total of 270 age-gender-ethnically matched subjects were genotyped by fluorescent-labelled restriction fragment length polymorphism, multiplex PCR, and fragment analysis. Sequencing was used to confirm the genotyping results. Expression of the full-length and soluble CTLA-4 mRNAs analysed using real-time PCR. Sera from subjects were screened for sCTLA-4 using ELISA. Tested subjects revealed ten alleles and sixteen genotypes of CTLA-4 3'UTR(AT)n. The 3'UTR(AT)n was significantly associated with HT: allele (AT)15 and genotype 15/15 were found to cause susceptibility to HT (P = 0.004, OR = 2.13, 95 % CI = 1.26-3.58 and P = 0.029, OR = 2.77, 95 % CI = 1.1-6.94, respectively), whereas allele (AT)6 and genotype 6/6 were found to be protective of HT (P = 0.00002, OR = 0.36, 95 % CI = 0.227-0.57 and P = 0.001, OR = 0.357, 95 % CI = 0.1980.64, respectively). SNP A49G and ICOS(GT)n revealed no significant association with HT (P > 0.05). The expression of sCTLA-4 was inversely proportional to the number of 3'UTR(AT)n repeats, with heterozygous and longer (AT)n repeats showing lower levels of sCTLA-4 mRNA than those with shorter alleles in HC and HT (P = 0.001 and P = 0.04, respectively). Significant increase in the serum level of sCTLA-4 was observed in HT patients compared with the HC (P = 0.0007). The novel finding in our study is that the CTLA-4 3'UTR(AT)n proven to be a key player in the pathogenesis of HT.
Medical principles and practice : international journal of the Kuwait University, Health Science Centre, 2017
To examine the concordance between lifestyle practices and beliefs of people living in Kuwait, an... more To examine the concordance between lifestyle practices and beliefs of people living in Kuwait, and between their lifestyle practices and established evidence-informed recommendations for health. A cross-sectional interview questionnaire study was conducted using a convenience sample of 100 adults living in Kuwait (age range 19-75 years). The interview included sections on demographics, and lifestyle-related practices and beliefs related to smoking, diet/nutrition, physical activity/exercise, sleep, and stress. Diet/nutrition and physical activity/exercise benchmarks were based on international standards. Analyses included descriptive statistics and the χ2 test. Beliefs about the importance of nutrition in lifestyle-related conditions were limited, and this was apparent in participants' dietary habits, e.g., low consumption of fruit/vegetables and multigrains: 16 (16%) and 9 (9%) met the recommended guidelines, respectively. Ninety-nine (99%) believed physical activity/exercise a...
The expression of interferon inducible genes are reported to be heightened in systemic lupus eryt... more The expression of interferon inducible genes are reported to be heightened in systemic lupus erythematosus (SLE); nevertheless, not much is known regarding the genetic variants underlying these genes and their role in the pathogenesis of disease. Herein, we aim to explore the potential association and contribution of polymorphisms in MX1 gene (i) promoter with part of exon 1 (ii) intron 6, and (iii) their resulting haplotypes, with susceptibility to SLE. A total of 306 subjects, 152 SLE and 154 healthy controls (HC), were screened by direct sequencing method. Statistical analysis was carried out using appropriate software. The screening region of interest in MX1 revealed the existence of promoter (−123C/A, −88G/T, −20 A/C) and intron 6 (+9862G/A, +10190G/A, +9901C/G, +9920C/A, +9959C/T, +10047A/G) variants in SLE and HC. A significant association was observed between MX1 −88G/T SNP and susceptibility to SLE (χ2 = 4.18, p = 0.04, OR = 1.89, 95 % CI 1.03–3.5). Haplotype analysis also revealed increased risk of SLE among individuals carrying CTA haplotype (−123 C, −88 T, −20 A) (χ2 = 5.74, p = 0.017, OR = 4.28, 95 % CI 1.30–14.06). None of the other tested variants showed any significant association with SLE. The present study is the first to reveal the influence of genetic variation in MX1 gene in susceptibility to SLE.
Abstract Introduction Autoimmunity is one of the top ten causes of morbidity and mortality in fem... more Abstract Introduction Autoimmunity is one of the top ten causes of morbidity and mortality in female children and young to middle aged woman, with similar prevalence rate across different geographic areas. About 5-30% of autoimmune patients are inclined to develop additional autoimmune diseases leading to the development of overlap diseases. An overlap between Lupus and Rheumatoid Arthritis (RA) referred to as Rhupus has been much on debate, whether it represents a single distinct entity or an overlap disease? Herein we reviewed the literature over the past 54 years to characterise rhupus subjects and to support the theory of overlap. Discussion Rhupus is known to be a complex musculoskeletal autoimmune disease defined by erosive polyarthritis. The exact cause and triggers of rhupus remains unknown with limited studies suggesting the combined role of genetic, immunological, hormonal and environmental factors in the progression of disease. Among genetic factors, HLA-DR alleles were s...
The global emergence of drug-resistant malarial parasites necessitates identification and charact... more The global emergence of drug-resistant malarial parasites necessitates identification and characterization of novel drug targets. Three reactions are involved in methylenetetrahydrofolate recycling: Thymidylate synthase (TS), dihydrofolate reductase (DHFR), and serine hydroxymethyltransferase (SHMT). Malarial bifunctional DHFR-TS is a well-studied, important target of established drugs such as pyrimethamine and cycloguanil. In sharp contrast, malarial SHMT remains largely uncharacterized. In the present study, a Plasmodium falciparum SHMT coding region was characterized. It had 1603 bp including two introns near the 5'-end of the gene: one 118 bp intron immediately after the start methionine and a 159 bp intron after an additional 34 amino acids. The three exons together coded for a 442 amino acid protein with 38-47% identity to SHMT sequences from other species. Expression of malarial SHMT coding sequence (minus the introns) into glyA mutants of Escherichia coli relieved glycine auxotrophy and permitted direct assay of SHMT catalytic activity in bacterial cell lysates. This is the first SHMT cloned and expressed from a protozoan parasite. The molecular tools developed in this study will be useful for developing potential antimalarials directed at SHMT.
Objectives: We aimed to investigate germline mutation in another extended von Hippel-Lindau (VHL)... more Objectives: We aimed to investigate germline mutation in another extended von Hippel-Lindau (VHL) family in Kuwait with Arabian and Persian genetic admixture. Materials andMethod: Polymerase chain reaction (PCR) followed by single-strand conformation polymorphism (SSCP) and direct sequencing of the PCR amplicons, that showed clear band shift, were used to screen the VHL gene in the index patient, 20 members of her family and 55 healthy controls of matching ethnicity. Result: The clinical history of all patients revealed multiple hemangioblastomas in various organs without pheochromocytomas. SSCP showed a clear band shift in 2 PCR amplicons, which were then sequenced. One was in the promoter region revealing a polymorphic site (A–123G) found as heterozygous in 40% of the healthy control subjects of the same ethnicity. The second band shift was in exon 2 seen in all clinically diagnosed VHL cases but not in the healthy members of the family or the screened healthy population. Direct s...
Objective: The objective of the present study was to determine whether saponin hemolysis could im... more Objective: The objective of the present study was to determine whether saponin hemolysis could improve microscopic detection of malaria parasites in human blood, since it has been previously reported that the technique has been used to enrich Plasmodium falciparum culture to ≧90% parasitemia. Material and Methods: Blood samples from suspected malaria cases were first examined in routine thick and thin smears under the microscope. The sample (1 ml) was then hemolyzed with 0.015% saponin in saline and centrifuged, the separated pellet was stained with Giemsa stain and examined microscopically, using PCR to confirm species identification. Results: With P. falciparum in vitro culture, the proportions of infected erythrocytes were approximately 0.7–2% before and 65–97% after saponin hemolysis, confirming published reports. In contrast, there was little or no increase in the proportions of intact infected erythrocytes after saponin hemolysis of clinical blood specimens. However, 20–600 he...
Objective: This study was undertaken to determine the prevalence of congenital cytomegalovirus (C... more Objective: This study was undertaken to determine the prevalence of congenital cytomegalovirus (CMV) infection in pregnant women at the end of pregnancy in Kuwait using cord blood and maternal urine. Subjects and Methods: Urine samples were collected prior to childbirth, and cord blood was collected immediately after delivery from 983 women. Anti-CMV IgG and IgM antibodies were determined using ELISA; CMV DNA was detected using nested PCR, and viral load was calculated using real-time PCR. CMV concentration in samples was categorized as low when the viral load ≤103 copies/µl, intermediate when the viral load = 103–104 copies/µl, and high when the viral load >104 copies/µl. The cord blood serology outcome was compared to cord blood PCR, cord blood viral load, maternal urine PCR and viral load analyses. Results: Serology showed that of the 983 cord blood samples, 89 (9%) were positive for anti-CMV IgM antibodies; PCR test showed 44 (4.5%) contained CMV DNA, and there was a high vir...
International Journal of Laboratory Hematology, 2010
SummaryHomozygous β‐thalassemia is a common genetic disorder in the Arabian Peninsula and an impo... more SummaryHomozygous β‐thalassemia is a common genetic disorder in the Arabian Peninsula and an important cause of morbidity in Kuwait. The anemia is so severe that chronic blood transfusions, and the resulting iron overload, cause a shift in immunoregulatory balances and a deficiency in zinc. It was reported that individual immunological profile of CD8+ T‐lymphocytes may have a modifying effect on the severity of iron overload in HFE homozygous hemochromatosis patients, with low numbers being negatively correlated with the total amount of body iron stores. This has not been tested in thalassemia major patients. This study was designed to utilize flow cytometric immunophenotyping to characterize effects of regular blood transfusion, and high serum ferritin levels because of irregular use of iron chelation therapy on T lymphocytes (CD2, CD3, CD4 and CD8), B lymphocytes (CD19) and natural killer cells (CD56) and zinc levels in the blood of patients with thalassemia major (n = 49) and hea...
SummaryDeoxyribonuclease I (DNASE1) may be responsible for the removal of DNA from nuclear antige... more SummaryDeoxyribonuclease I (DNASE1) may be responsible for the removal of DNA from nuclear antigens at sites of high cell turnover, thus preventing the onset of systemic lupus erythematosus (SLE). The purpose of this study was to screen DNASE1 gene for mutations that may have an effect on susceptibility to develop SLE. DNA was extracted from 76 Kuwaiti SLE patients and 92 race‐matched controls. PCR‐direct sequencing was used to screen DNASE1 promoter, coding sequence and exon–intron boundaries for mutation. Association of genomic variations was assessed using a Chi‐square test. Molecular analysis of the DNASE1 gene did not reveal any mutation. However, a 56‐bp repeat was detected in intron4 which was previously reported and named HumDN1. The allelic and genotypic distributions of the HumDN1 VNTR were compared between SLE patients and healthy subjects. Alleles were denoted as 2, 3, 4, 5 and 6 corresponding to the number of repeats of the 56 bp unit. Alleles 4, 5, and 6 showed signifi...
ABSTRACT Members of arrestin/beta-arrestin protein family are thought to participate in agonist-m... more ABSTRACT Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors, including rhodopsin and beta2-adrenergic receptor. Unlike in human and cow, splice variants of this protein family in rat have not been studied extensively, and there has been no report on their existence at protein level. Hence, a previous report by others on the localization of both beta-arrestin-1 and -2 in a wide range of innervated rat tissues could imply their broad receptor specificity. In this report we show the presence of two alternatively spliced forms of beta-arrestin-1 in several rat tissues using both reverse transcription-polymerase chain reaction and Western immunoblot. Splicing of beta-arrestin-1 pre-mRNA appears to be subject to differential regulation between the rat CNS and peripheral tissues. In contrast, we detected no splice variants of beta-arrestin-2 in rat. A comparison of the genomic DNA sequences of bovine and rat beta-arrestin-2, where the splicing of bovine beta-arrestin-2 mRNA has been reported, revealed a high degree of homology in their organization of exons and introns as well as certain differences that might be responsible for the different processing of beta-arrestin-2 mRNA in the two species. Our two-dimensional isoelectric focusing gels using rat spinal cord and heart tissues demonstrate isoelectric heterogeneity of rat beta-arrestin-1, suggesting that beta-arrestin-1 is subject to post-translational modification unlike beta-arrestin-2.
Analysing two CTLA-4 markers [exon 1 A49G single nucleotide polymorphism (SNP) and exon 4 3&a... more Analysing two CTLA-4 markers [exon 1 A49G single nucleotide polymorphism (SNP) and exon 4 3'UTR (AT)n repeat] and the ICOS intron 4 (GT)n marker for their potential association with HT, and exploring the effect of the tested SNPs on the CTLA-4 isoform expression at the mRNA and protein levels. Total of 270 age-gender-ethnically matched subjects were genotyped by fluorescent-labelled restriction fragment length polymorphism, multiplex PCR, and fragment analysis. Sequencing was used to confirm the genotyping results. Expression of the full-length and soluble CTLA-4 mRNAs analysed using real-time PCR. Sera from subjects were screened for sCTLA-4 using ELISA. Tested subjects revealed ten alleles and sixteen genotypes of CTLA-4 3'UTR(AT)n. The 3'UTR(AT)n was significantly associated with HT: allele (AT)15 and genotype 15/15 were found to cause susceptibility to HT (P = 0.004, OR = 2.13, 95 % CI = 1.26-3.58 and P = 0.029, OR = 2.77, 95 % CI = 1.1-6.94, respectively), whereas allele (AT)6 and genotype 6/6 were found to be protective of HT (P = 0.00002, OR = 0.36, 95 % CI = 0.227-0.57 and P = 0.001, OR = 0.357, 95 % CI = 0.1980.64, respectively). SNP A49G and ICOS(GT)n revealed no significant association with HT (P > 0.05). The expression of sCTLA-4 was inversely proportional to the number of 3'UTR(AT)n repeats, with heterozygous and longer (AT)n repeats showing lower levels of sCTLA-4 mRNA than those with shorter alleles in HC and HT (P = 0.001 and P = 0.04, respectively). Significant increase in the serum level of sCTLA-4 was observed in HT patients compared with the HC (P = 0.0007). The novel finding in our study is that the CTLA-4 3'UTR(AT)n proven to be a key player in the pathogenesis of HT.
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