Evaluation of the association between OPA1 polymorphisms andprimary open-angle glaucoma in Barbados families

[摘要] Purpose: To investigate whether single nucleotide polymorphisms(SNPs) in the OPA1 gene are associated with two primary open-angleglaucoma (POAG) subgroups: those with elevated intraocular pressure(POAG/IOP) and those with normal tension glaucoma (NTG) in theAfrican-Caribbean population of Barbados, West Indies.Methods: SNPs at intervening sequence (IVS) 8, +4, and +32 of theOPA1 gene were directly sequenced from 48 individuals with POAG/IOP,48 nonglaucomatous controls, and 61 people with NTG. The remaining exonsof OPA1 were screened for sequence variations in the same 48POAG/IOP participants and 48 controls by denaturing high performanceliquid chromatography (dHPLC), and identified variations were confirmedby bidirectional sequencing. Genotype and allele frequencies of all SNPswere compared for statistically significant differences using theχ2 and Fisher's exact test. Haplotypes and compound genotypeswere also analyzed to evaluate the combined effect of the two IVS8SNPs.Results: The analyses of the genotype and haplotype frequencies ofIVS8 +4 and +32 do not show statistically significant differencesbetween those with POAG/IOP or NTG and controls. At IVS8 +32, althoughthere are suggestions of possible associations of the CC genotype withNTG (χ2=3.81, p=0.05), and the TC genotype with POAG/IOP(χ2=4.23, p=0.04), these differences do not reach statisticalsignificance at the level of 0.017 after a Bonferroni correction. Inaddition, the combined genotype comparisons at IVS8 +32 do not supportthe association (for controls compared to NTG χ2=4.19, p=0.12,df=2; and for controls compared to POAG χ2=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 beassociated with POAG/IOP.Conclusions: Although some results are suggestive, there is notsufficient evidence to support an association of the SNPs evaluated inOPA1 with POAG/IOP or NTG in the African-Caribbean population ofBarbados, West Indies.

[学科分类] 生物化学/生物物理