CDKN2B-AS1 associations with Primary Open-Angle Glaucoma related features in Chinese patients from Singapore

Abstract

Purpose: Genetic variants at the 9q21 locus mapping near cyclin-dependent kinase inhibitor 2B antisense noncoding RNA (CDKN2B-AS1) were shown to be strongly associated with primary open angle glaucoma (POAG) in several independent studies. We now aim to assess the association between the strongly associated POAG variants in this region and glaucoma related traits in Singaporean Chinese patients.

Methods: 1,245 POAG patients were recruited from Singapore National Eye Center. All patients were genotyped for 4 single nucleotide polymorphisms (SNPs) at CDKN2B-AS1 (rs2157719, rs564398, rs7865618, rs1412829). We measured the association between each SNP marker and glaucoma related traits such as vertical cup disc ratio (VCDR), presenting intraocular pressure (IOP), visual field mean deviation (VFMD), and central corneal thickness (CCT) using linear regression under an additive model.

Results: All four SNP markers genotyped were in high linkage disequilibrium (pair-wise r² > 0.8). We observed nominally significant associations (P < 0.05) with these CDKN2B-AS1 SNP markers and VCDR (rs2157719, β=-0.03 units per copy of the minor allele, P = 0.018), IOP (rs2157719, β= 1.5mmHg increase per copy of the allele, P = 0.02), as well as VFMD (rs2157719, β=1.69 units, P = 0.044). We did not observe any evidence of association between CDKN2B-AS1 SNP markers and CCT (P > 0.5 for all comparisons).

Conclusions: Nominal evidence of association was observed between common genetic polymorphism at CDKN2B-AS1 and POAG related endophenotypic traits in a Singaporean Chinese POAG collection comprising 1,245 patients. Intriguingly, patients who carry the effect allele protective against POAG showed a trend of association towards lower VCDR despite having higher IOP. Our findings should be followed up in other independent POAG collections for further verification.

Keywords: 539 genetics • 627 optic disc • 440 candidate gene analysis