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

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: AFAP1 rs938604 (P_meta =6.40×10^-5, OR=0.70), FNDC3B rs62283813 (P_meta =0.0050, OR=1.24) and GAS7 rs9913911 (P_meta =0.0060, OR=1.19). In subgroup analysis, these three SNPs showed stronger association with HTG: AFAP1 rs938604 (P_meta =8.00×10^-6, OR=0.59), FNDC3B rs62283813 (P_meta =6.00×10^-7, OR=1.55) and GAS7 rs9913911 (P_meta =0.0040, OR=1.24). In addition, SPRED2 rs4414666 (P_meta =8.00×10^-4, OR=1.29) was also significantly associated with HTG. No SNP showed a significant association with NTG.

This study confirms AFAP1 rs938604, FNDC3B rs62283813, GAS7 rs9913911 and SPRED2 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.