To investigate the lysyl oxidase-like 1 (LOXL1) gene for single nucleotide polymorphism (SNP) var... more To investigate the lysyl oxidase-like 1 (LOXL1) gene for single nucleotide polymorphism (SNP) variations in Japanese patients with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) and to examine the phenotypes of the patients with these variations. Fifty-six unrelated Japanese patients with XFS, including 36 patients with XFG, were studied. Genomic DNA was extracted from the leukocytes of peripheral blood, and three SNPs (rs1048661; p.Arg141Leu, rs3825942; p.Gly153Asp, and rs2165241) were identified. These SNPs were amplified by polymerase chain reaction (PCR), directly sequenced, and genotyped. Two nonsynonymous variants in exon 1 of LOXL1,rs1048661 and rs3825942, were found to be strongly associated with XFS including XFG. The frequency of the T allele (0.964) in rs1048661 in eyes with XFS was much higher in controls (0.507) with a p value of 7.7x10(-18). The odds ratio for the T allele in rs1048661 was 26.0 (95% confidence interval, 18.3-37.1). In the haplotype analysis,...
The human trabecular meshwork and ciliary body, which express beta-adrenergic receptors (ADRB1 an... more The human trabecular meshwork and ciliary body, which express beta-adrenergic receptors (ADRB1 and ADRB2), control aqueous humor dynamics. We investigated associations of ADRB polymorphisms with open-angle glaucoma (OAG), because ADRB gene polymorphisms alter receptor function. We studied 240 Japanese controls and 505 Japanese OAG patients including 211 with primary open-angle glaucoma (POAG), and 294 with normal-tension glaucoma (NTG). Associations of four polymorphisms (Ser49Gly and Arg389Gly in the ADRB1 gene; Arg16Gly and Gln27Glu in the ADRB2 gene) were compared between patients and controls. Age, intraocular pressure (IOP), and visual field defects at diagnosis were examined for associations with polymorphisms. The Arg389Gly polymorphism in the ADRB1 gene showed significantly different allele and genotype frequencies in patients with NTG than in controls (p = 0.004 and 0.006, respectively). Other polymorphisms did not show a significant frequency difference. In POAG patients, ...
Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease wi... more Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3,504 POAG cases and 9,746 controls with replication of the most significant findings in 9,173 POAG cases and 26,780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], Odds Ratio [OR] =0.71, P=2.81x10(-33)), we observed one SNP showing significant association to POAG (CDC7 - TGFBR3 rs1192415, ORG-allele =1.13, Pmeta=1.60 x 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.
To investigate the lysyl oxidase-like 1 (LOXL1) gene for single nucleotide polymorphism (SNP) var... more To investigate the lysyl oxidase-like 1 (LOXL1) gene for single nucleotide polymorphism (SNP) variations in Japanese patients with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) and to examine the phenotypes of the patients with these variations. Fifty-six unrelated Japanese patients with XFS, including 36 patients with XFG, were studied. Genomic DNA was extracted from the leukocytes of peripheral blood, and three SNPs (rs1048661; p.Arg141Leu, rs3825942; p.Gly153Asp, and rs2165241) were identified. These SNPs were amplified by polymerase chain reaction (PCR), directly sequenced, and genotyped. Two nonsynonymous variants in exon 1 of LOXL1,rs1048661 and rs3825942, were found to be strongly associated with XFS including XFG. The frequency of the T allele (0.964) in rs1048661 in eyes with XFS was much higher in controls (0.507) with a p value of 7.7x10(-18). The odds ratio for the T allele in rs1048661 was 26.0 (95% confidence interval, 18.3-37.1). In the haplotype analysis,...
The human trabecular meshwork and ciliary body, which express beta-adrenergic receptors (ADRB1 an... more The human trabecular meshwork and ciliary body, which express beta-adrenergic receptors (ADRB1 and ADRB2), control aqueous humor dynamics. We investigated associations of ADRB polymorphisms with open-angle glaucoma (OAG), because ADRB gene polymorphisms alter receptor function. We studied 240 Japanese controls and 505 Japanese OAG patients including 211 with primary open-angle glaucoma (POAG), and 294 with normal-tension glaucoma (NTG). Associations of four polymorphisms (Ser49Gly and Arg389Gly in the ADRB1 gene; Arg16Gly and Gln27Glu in the ADRB2 gene) were compared between patients and controls. Age, intraocular pressure (IOP), and visual field defects at diagnosis were examined for associations with polymorphisms. The Arg389Gly polymorphism in the ADRB1 gene showed significantly different allele and genotype frequencies in patients with NTG than in controls (p = 0.004 and 0.006, respectively). Other polymorphisms did not show a significant frequency difference. In POAG patients, ...
Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease wi... more Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3,504 POAG cases and 9,746 controls with replication of the most significant findings in 9,173 POAG cases and 26,780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], Odds Ratio [OR] =0.71, P=2.81x10(-33)), we observed one SNP showing significant association to POAG (CDC7 - TGFBR3 rs1192415, ORG-allele =1.13, Pmeta=1.60 x 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.
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