The association between CAV1/2 region loci and their relation with primary open angle glaucoma

Abstract

Purpose: To assess the association between single nucleotide polymorphisms (SNPs) in the CAV1/2 region in relation to primary open angle glaucoma (POAG) in two genome-wide association studies with imputed data.

Methods: We measured the association between 70 SNPs located within 50kb of the CAV1/2 region in two large POAG datasets, the Glaucoma Genes and Environment (GLAUGEN) study (976 cases, 1140 controls) and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium (2032 cases, 2290 controls). Genotyping was performed on the Illumina Human 660WQuadv1C BeadChip array and imputed to 2.5 million markers with MACH using the HapMap 2.3 reference panel. We used logistic regression models of POAG in the overall population and in men and women separately, and we conducted secondary analyses of POAG subtypes defined by intraocular pressure (IOP) and visual field (VF) defect. Results from each dataset were meta-analyzed with the METAL software package. A Bonferroni corrected significance level of 7.14x10-4 was used to account for the 70 SNPs tested.

Results: We found significant associations between ten CAV1/2 SNPs and POAG (top SNP rs4236601 pooled p=1.7x10-7). One significant association was observed among women (top SNP rs4236601 pooled p=1.19x10-5) but none in men (top SNP rs17588172 pooled p=1.82x10-3). When the outcome was stratified by type of VF loss, five CAV1/2 SNPs were associated with POAG with paracentral VF loss only (top SNP rs17588172 pooled p=1.14x10-4) and none with POAG with peripheral VF loss only (top SNP rs4236601 pooled p=8.59x10-4). There were two SNPs associated with normal tension glaucoma (NTG) overall (top rs10270569 pooled p=5.08x10-4) and one SNP associated with NTG among men (rs10270569 pooled p=6.93x10-4) but not among women. There were no significant SNPs in relation to high tension POAG (HTG) overall or stratified by gender.

Conclusions: Within our dataset, CAV1/2 SNPs were significantly associated with POAG overall, particularly among women. CAV1/2 SNPs were also significantly associated with POAG cases with only paracentral visual field defects and with normal tension glaucoma. These data affirm the potential role of CAV1/2 in POAG and indicate that CAV1/2 may have differing effects on POAG pathogenesis by gender and by type of visual field defect.

Keywords: 464 clinical (human) or epidemiologic studies: risk factor assessment • 539 genetics • 758 visual fields