Genotype–Phenotype Correlation Analysis for Three Primary Angle Closure Glaucoma-Associated Genetic Polymorphisms

Abstract

Recently, three genetic susceptibility loci for primary angle closure glaucoma (PACG) were identified: COL11A1 rs3753841, PCMTD1-ST18 rs1015213, and PLEKHA7 rs11024102. The purpose of this study was to investigate whether these single nucleotide polymorphisms (SNPs) affect the phenotype of PACG patients. A retrospective analysis was performed for 700 Singaporean Chinese PACG patients who had been genotyped. The associations between the three SNPs and clinical features related to severity of glaucoma were studied. For a subgroup of patients who had ≥ 5 years of follow-up and ≥ 5 reliable visual field (VF) tests, differences in glaucoma progression, as measured by the proportion of VF progression and blindness, were compared among groups with different genotypes. The minor allele frequencies at COL11A1 rs3753841, PCMTD1-ST18 rs1015213, and PLEKHA7 rs11024102 were 36%, 2.1%, and 41.5%, respectively. There were no significant differences in sex, diagnosis (acute primary angle closure [APAC] versus non-APAC), age at diagnosis, laterality of glaucoma, or need for filtration surgery among patients with different genotypes (all P > 0.05). We also found no significant difference between genotypes and the IOP at presentation, and other clinical characteristics at DNA collection (vertical cup-to-disc ratio, best corrected visual acuity, baseline VF mean deviation, or pattern standard deviation). For the subgroup analysis, we did not observe significant associations between VF progression and the proportion of blindness with any of the PACG susceptibility loci. The three genetic susceptibility loci for PACG did not underlie any major phenotypic diversity in terms of disease severity or progression.