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Mona S. Awadalla, Kathryn P. Burdon, Jamie E. Craig; Candidate Gene Association Studies of Primary Angle Closure Glaucoma in the Australian Population. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4508.
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Glaucoma is the second leading cause of blindness worldwide, with primary angle closure glaucoma (PACG) accounting for about half of glaucoma blindness. The molecular mechanisms of PACG are unknown but there is likely to be a genetic component with familial clustering observed. Herein we investigate the association of four candidate genes; Cytochrome P4501B1 (CYP1B1), endothelial nitric oxide synthase(eNOS), serine protease 56(PRSS56) and neurotrophin 4 (NTF4) with PACG in the Caucasian Australian population. These genes have been reported to be associated with various forms of glaucoma or angle closure in other populations.
A total of 200 patients with angle closure were recruited through the Australian and New Zealand Registry of Advanced Glaucoma and classified according to the Foster classification, along with 288 examined normal controls. DNA was extracted from peripheral whole blood. Tag single nucleotide polymorphisms (SNPs) were selected to cover the majority of known common variation in Caucasians reported in HapMap within the candidate genes. SNPs were genotyped on the Sequenom platform. Allelic, genotypic and haplotypic association was analysed using PLINK.
Three eNOS SNPs, rs3793342 (p=0.002), rs7830 (p=0.011 and rs3918188 (p=0.013) were significantly associated with PACG in this Australian cohort. The eNOS haplotype was also significantly associated (omnibus p=0.01), with the CGCAATC haplotype giving a specific p-value of 0.005 and odds ratio of 1.4 (95%CI=0.9 - 2.1). In the PRSS56 gene, we observed a borderline significant association of two SNPs, rs1867778 (p=0.06) and rs13408229 (p=0.08), and the GGCGGC haplotype also demonstrated suggestive association with a p-value of 0.08, and odds ratio of 1.6 (95%CI=0.9 - 3.0). No association was observed with CYP1B1 or NTF4.
The results from this study demonstrate an association of PACG with SNPs in the eNOS gene in the Australian patients, which is consistent with the findings in a Pakistani cohort, but not in Chinese population. The PRSS56 gene shows a trend towards association but requires further investigation in a larger cohort to definitively detect an effect in this complex disease.
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