CDKN2BAS DNA Sequence Variants Are Associated with Exfoliation Glaucoma

Abstract

Purpose: : The CDKN2BAS polymorphisms have been associated with optic nerve cup-to-disc ratio (CDR), primary open angle glaucoma (POAG), particularly normal-tension glaucoma (NTG), suggesting that these SNPs primarily influence the development of optic nerve disease in glaucoma. In this study we evaluated the association of SNPs located in the CDKN2BAS genomic region with exfoliation syndrome (ES) and exfoliation glaucoma (EG) to determine if these SNPs also contribute to optic nerve disease in other types of glaucoma.

Methods: : Three SNPs located in the CDKN2BAS genomic region, rs1063192, rs2157719 and rs1412829, which have been previously associated with CDR, POAG and NTG, were analyzed in 196 Caucasian patients with ES and 2,655 controls. Among 196 patients with ES, 104 had glaucoma (EG) defined by characteristic visual field defects consistent with glaucomatous optic neuropathy on reliable tests. Single-SNP associations were initially analyzed using the chi-square test and further evaluated using logistic regression models adjusted for age.

Results: : All 3 SNPs were significantly associated with ES (p<0.008). The minor allele frequency of the top hit SNP rs1412829 was significantly lower in patients with ES than in controls (0.34 vs. 0.42; p=0.002, OR=0.71, 95%CI: 0.57-0.89). Subgroup analysis showed that this association only existed in EG (p<0.0009) but not in ES patients without glaucoma (ENG) (p>0.47). The minor allele frequency of the top hit SNP rs1412829 was significantly lower in patients with EG than in controls (0.29 vs. 0.42; p=0.0004, OR=0.58, 95%CI: 0.42-0.78). After adjusting for age, all these SNPs remained significantly associated with ES (p<0.01) and EG (p<0.002) but not with ENG (p>0.52). The associations with ES and EG survived multiple testing correction.

Conclusions: : These results suggest that CDKN2BAS SNPs contribute to optic nerve disease in exfoliation glaucoma, and thus may be risk factors for optic nerve disease in other common forms of glaucoma.

Keywords: genetics • candidate gene analysis • optic nerve