Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. This study proposed to screen candidate PACG-associated variants in Chinese Han people. Whole exome sequencing was applied to five confirmed PACG patients and two primary angle closure suspect individuals within a PACG-enriched Chinese Han family. A series of bioinformatics analyses were implemented to obtain high-risk single nucleotide variant (SNV) loci for PACG, which were subsequently used for linkage analysis for identifying linkage genome regions. In addition, MassARRAY SNV genotyping was applied to high-risk PACG loci as well as those within linkage regions in another independent cohort including 251 PACG and 251 normal samples to further screen high-confidence SNVs. A total of 27 loci in 19 genes remained after linkage analysis. The 19 genes were significantly enriched in biological processes tightly related to PACG, including retinol metabolism and salmonella infection. Two nonsynonymous SNV loci, rs897804 in exon15 of HOOK2 and rs3745193 in exon7 of GTPBP3, were recognized with higher variant frequency in PACG samples than that in control samples after association analysis of MassARRAY SNV genotyping data. This study sheds new light on the understanding of PACG incidence among Chinese Han people.
Keywords: GTPBP3; HOOK2; Han Chinese; primary angle closure glaucoma; rs3745193; rs897804.