Association of WDR36 polymorphisms with primary open-angle glaucoma

Abstract

Background: Various genes contribute to the pathophysiology of primary open-angle glaucoma (POAG). The WD repeat domain 36 (WDR36) gene may participate in T cell activation and, hence, in the pathogenesis of POAG. We investigated the association of two WDR36 gene single nucleotide polymorphisms (SNPs) with POAG. Methods: This cross-sectional study recruited patients aged >40 years with POAG and investigated the rs10038177 and rs1971050 SNPs of WDR36 using polymerase chain reaction and direct DNA sequencing. All participants underwent comprehensive ocular examination, visual field assessment using the Swedish Interactive Threshold Algorithm standard 24-2 threshold test, and measurement of peripapillary retinal nerve fiber layer thickness (RNFLT) using spectral domain optical coherence tomography. Results: We enrolled 105 patients with a mean (standard deviation) age of 55.41 (8.56) years and a male-to-female ratio of 56 (53.3%) to 49 (46.7%), most of whom had a diagnosis of POAG for 2 to 5 years (60.0%). Most participants had diabetes (90.5%) but not hypertension (88.6%). There was a significant association of rs10038177 (P<0.05), but not rs1971050 (P>0.05), with family history of glaucoma. The association between rs10038177 and intraocular pressure was significant (P<0.05), but that between rs1971050 and intraocular pressure was not (P>0.05). No significant association was observed between mean cup-to-disc ratio and either SNP (both P>0.05). For rs10038177, a significant association was found only with the RNFLT of the superior quadrant (P<0.05), whereas for rs1971050, a significant association was found with the RNFLT of all four quadrants and average RNFLT (all P<0.05). However, pairwise comparisons revealed no significant differences between genotypes (P>0.05 for all pairwise comparisons). The association of rs10038177 with glaucoma severity was insignificant (P>0.05), and most patients with the TC genotype (71.7%) had moderate severity. There was no significant association between rs1971050 and glaucoma severity (P>0.05). Conclusions: We observed genetic links between some, but not all, characteristics of POAG and the rs10038177 and rs1971050 SNPs of WDR36. Follow-up studies on these and other WDR36 SNPs in populations with different genetic backgrounds are necessary to confirm this genetic association.