Evaluation of the association between OPA1 polymorphisms and primary open-angle glaucoma in Barbados families.

PURPOSE To investigate whether single nucleotide polymorphisms (SNPs) in the OPA1 gene are associated with two primary open-angle glaucoma (POAG) subgroups: those with elevated intraocular pressure (POAG/IOP) and those with normal tension glaucoma (NTG) in the African-Caribbean population of Barbados, West Indies. METHODS SNPs at intervening sequence (IVS) 8, +4, and +32 of the OPA1 gene were directly sequenced from 48 individuals with POAG/IOP, 48 nonglaucomatous controls, and 61 people with NTG. The remaining exons of OPA1 were screened for sequence variations in the same 48 POAG/IOP participants and 48 controls by denaturing high performance liquid chromatography (dHPLC), and identified variations were confirmed by bidirectional sequencing. Genotype and allele frequencies of all SNPs were compared for statistically significant differences using the chi2 and Fisher's exact test. Haplotypes and compound genotypes were also analyzed to evaluate the combined effect of the two IVS8 SNPs. RESULTS The analyses of the genotype and haplotype frequencies of IVS8 +4 and +32 do not show statistically significant differences between those with POAG/IOP or NTG and controls. At IVS8 +32, although there are suggestions of possible associations of the CC genotype with NTG (chi2 = 3.81, p = 0.05), and the TC genotype with POAG/IOP (chi2 = 4.23, p = 0.04), these differences do not reach statistical significance at the level of 0.017 after a Bonferroni correction. In addition, the combined genotype comparisons at IVS8 +32 do not support the association (for controls compared to NTG chi2 = 4.19, p = 0.12, df = 2; and for controls compared to POAG chi2 = 4.83, p = 0.09, df = 2). Sixteen variants are observed in the OPA1 gene, of which 10 are novel. Neither genotype nor allele frequencies of any SNP are found to be associated with POAG/IOP. CONCLUSIONS Although some results are suggestive, there is not sufficient evidence to support an association of the SNPs evaluated in OPA1 with POAG/IOP or NTG in the African-Caribbean population of Barbados, West Indies.