Strong Association of SLC24A1 at GLCN1 With Susceptibility to Primary Open Angle Glaucoma

Abstract

Purpose:: Our previous genome-wide scan and further fine mapping identified a novel locus at 15q22-q24 (GLC1N) in one Chinese family affected with juvenile onset primary open angle glaucoma (JOAG). In the present study, we attempted a case-control association study by gene-based SNPs to search for POAG associated genes at GLC1N.

Methods:: A total of 122 gene-based SNPs within GLC1N were genotyped in 97 unrelated JOAG patients and 99 unrelated control subjects using the TaqMan technology. Single marker association analysis and haplotype analysis were performed to investigate the association between the SNPs and JOAG. Stepwise logistic regression analysis of the significantly associated SNPs was used to determine whether their effects are independent. In addition, one non-synonymous SNP in the SLC24A1 gene which was significantly associated with JOAG was genotyped in all family members of the JOAG family from whom GLC1N was originally identified.

Results:: A set of 6 adjacent SNPs spanning 0.55 Mb within GLC1N were significantly associated with JOAG. The risk alleles of these SNPs conferred increased risk of JOAG. Only one SNP in SLC24A1 was still significantly associated with JOAG (P = 0.0045) after stepwise logistic regression analysis. One haplotype of SLC24A1 conferred 2.32 (95%CI: 1.32-4.09) fold of increased risk to JOAG. In the JOAG family, the risk allele of non-synonymous SNP in SLC24A1 was inherited by all 8 affected subjects and 6 other at-risk family members. But three unaffected spouses also carried one copy of the risk allele. Therefore this non-synonymous SNP did not completely segregate with JOAG in this family.

Conclusions:: Our findings indicated that the mutation in other regions of SLC24A1 may be responsible for JOAG in this family, or another gene in this region may be the actual cause of glaucoma.

Keywords: genetics