Association of polymorphisms in 17 loci with primary open-angle glaucoma in Chinese and Japanese.

Abstract

To evaluate the associations of single-nucleotide polymorphisms (SNPs) in 17 loci with primary open-angle glaucoma (POAG) and subtypes in Chinese and Japanese. 17 SNPs in 17 genes, selected from a recent genome-wide association study, were genotyped in a Hong Kong Chinese cohort of 1093 POAG patients, including 557 high-tension glaucoma (HTG) and 536 normal-tension glaucoma (NTG) patients, and 584 controls. Seven SNPs showing association in the Hong Kong cohort were genotyped in a Shantou Chinese cohort of 155 POAG patients and 380 controls and an Osaka Japanese cohort of 254 POAG patients and 207 controls. The SNP-disease association of individual and pooled cohorts was analysed. In combined Chinese and Japanese subjects, three SNPs were significantly associated with POAG: <i>AFAP1</i> rs938604 (<i>P_meta</i> =6.40×10^-5, OR=0.70), <i>FNDC3B</i> rs62283813 (<i>P_meta</i> =0.0050, OR=1.24) and <i>GAS7</i> rs9913911 (<i>P_meta</i> =0.0060, OR=1.19). In subgroup analysis, these three SNPs showed stronger association with HTG: <i>AFAP1</i> rs938604 (<i>P_meta</i> =8.00×10^-6, OR=0.59), <i>FNDC3B</i> rs62283813 (<i>P_meta</i> =6.00×10^-7, OR=1.55) and <i>GAS7</i> rs9913911 (<i>P_meta</i> =0.0040, OR=1.24). In addition, <i>SPRED2</i> rs4414666 (<i>P_meta</i> =8.00×10^-4, OR=1.29) was also significantly associated with HTG. No SNP showed a significant association with NTG. This study confirms <i>AFAP1</i> rs938604, <i>FNDC3B</i> rs62283813, <i>GAS7</i> rs9913911 and <i>SPRED2</i> rs4414666 as HTG-specific loci in Chinese and Japanese populations. These findings provide new insights into the genetic architecture of POAG, highlighting distinct molecular mechanisms between HTG and NTG subtypes.