Genetics In Glaucoma patients of African descent study (GIGA): Known genetic risk factors for Primary Open Angle Glaucoma in a South African population

摘要

Purpose : Primary open angle glaucoma (POAG) is the predominant type of glaucoma worldwide. Its prevalence varies greatly among ethnic groups, and is the highest in black African populations (2-7%). Surprisingly, worldwide endeavours to elucidate the genetic complexity of POAG have not incorporated Sub Saharan African (SSA) populations. To fill this gap, we established a cohort of SSA POAG cases for genetic testing. We investigated the association of known POAG risk loci and genes in our multi ancestry cohort of self-identified black South Africans and admixed individuals from South Africa. Methods : 104 black South Africans (80 POAG cases and 24 controls) and 154 admixed South Africans (98 POAG cases and 56 controls) were recruited from the division of Ophthalmology Groote Schuur Hospital in Cape Town South Africa. Genotyping was performed using the Illumina HumanOmniExpressExome Beadchip, which assesses 950.000 SNPa??s including ~273.000 functional exonic markers. The association between genotypes and susceptibility to POAG was tested using logistic regression analysis assuming an additive genetic model, adjusting for age, gender and 10 principal components. First, we evaluated 33 POAG risk variants identified in previously associated Genome Wide Association Studies (GWAS) in European and Asian ancestry. Second, we performed a gene-based test on 18 known POAG genes using VEGAS2 software. Results : A total of 258 subjects (178 POAG cases, 80 controls) successfully passed quality control and were included in this analysis. Focusing on the 33 POAG risk variants, we observed nominally significant associations (Pa?¤0.05) for rs7518099 located in the TMCO1 region (P= 0.02) and rs4236601 located in the CAV/CAV2 region (P= 0.04). With respect to the gene-based analysis, we found a significant association with the CAV2 gene (P=0.0016) after Bonferroni correction for multiple testing (P=0.0028). Conclusions : Our results suggest that variants in several genes associated with POAG in Europeans and Asians also play a role in POAG patients from South Africa. In particular CAV2, a gene which appears to have a role in intraocular pressure regulation, is a robust POAG gene which merits further functional characterization. This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.