Association of eNOS polymorphisms with primary angle-closure glaucoma

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Awadalla, Mona S
Thapa, Suman S
Hewitt, Alex W
Craig, Jamie E
Burdon, Kathryn Penelope
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Association for Research in Vision and Ophthalmology
Copyright 2013 The Association for Research in Vision and Ophthalmology, Inc.
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Association for Research in Vision and Ophthalmology
Purpose: Recently, several studies have investigated genetic associations between Cytochrome P450 (CYP1B1), Endothelial nitric oxide synthase (eNOS) and Neurotrophin-4 (NTF4) with primary angle-closure glaucoma (PACG) in various ethnic groups. Here we investigate the association of these candidate genes with PACG in samples from Australia and Nepal. Method: A total of 235 patients with PACG (106 Nepalese and 129 Australian) and 492 controls (204 Nepalese and 288 Australian) were included. Tag single nucleotide polymorphisms (SNPs) were selected to cover the majority of common variation within the candidate genes and genotyped in DNA extracted from peripheral whole blood. Allele and haplotype analyses were conducted in PLINK. Bonferroni correction was applied for the total number of SNPs in this study (p=0.05/15=0.003) Results: In the Australian cohort, one eNOS SNP rs3793342 shows significance association with PACG in the Australian cohort after Bonferroni correction (p-value 0.003, OR 0.5 95% CI 0.3-0.8). After adjusting the results for sex and age both SNPs rs3793342 and rs7830 showed significance after Bonferroni correction (p-value of 0.001 and 0.003, respectively). The eNOS haplotype of all 7 typed SNPs showed significant association with a global p-value of 0.019, with the CGCAATC haplotype giving a specific p-value of 0.008 and odds ratio of 1.5 (95% CI 0.9-2.4). In the Nepalese cohort, SNPs in CYP1B1 and NTF4 genes showed borderline association with PACG but did not survive Bonferroni correction. Conclusions: The present data support the involvement of common variations in eNOS with PACG pathogenesis. Differences were observed in the two populations studied, and additional replication studies in other populations are necessary to confirm these associations
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Awadalla MS, Thapa SS, Hewitt AW, Craig JE, Burdon KP. Association of eNOS polymorphisms with primary angle-closure glaucoma. Investigative Ophthalmology & Visual Science .2013 Mar 1;54(3):2108-14