Association of WDR۳۶ polymorphisms with primary open-angle glaucoma

Abstract Background: Various genes contribute to the pathophysiology of primary open-angle glaucoma (POAG). The WD repeat domain ۳۶ (WDR۳۶) gene may participate in T cell activation and, hence, in the pathogenesis of POAG. We investigated the association of two WDR۳۶ gene single nucleotide polymorphisms (SNPs) with POAG. Methods: This cross-sectional study recruited patients aged >۴۰ years with POAG and investigated the rs۱۰۰۳۸۱۷۷ and rs۱۹۷۱۰۵۰ SNPs of WDR۳۶ using polymerase chain reaction and direct DNA sequencing. All participants underwent comprehensive ocular examination, visual field assessment using the Swedish Interactive Threshold Algorithm standard ۲۴-۲ threshold test, and measurement of peripapillary retinal nerve fiber layer thickness (RNFLT) using spectral domain optical coherence tomography. Results: We enrolled ۱۰۵ patients with a mean (standard deviation) age of ۵۵.۴۱ (۸.۵۶) years and a male-to-female ratio of ۵۶ (۵۳.۳%) to ۴۹ (۴۶.۷%), most of whom had a diagnosis of POAG for ۲ to ۵ years (۶۰.۰%). Most participants had diabetes (۹۰.۵%) but not hypertension (۸۸.۶%). There was a significant association of rs۱۰۰۳۸۱۷۷ (P<۰.۰۵), but not rs۱۹۷۱۰۵۰ (P>۰.۰۵), with family history of glaucoma. The association between rs۱۰۰۳۸۱۷۷ and intraocular pressure was significant (P<۰.۰۵), but that between rs۱۹۷۱۰۵۰ and intraocular pressure was not (P>۰.۰۵). No significant association was observed between mean cup-to-disc ratio and either SNP (both P>۰.۰۵). For rs۱۰۰۳۸۱۷۷, a significant association was found only with the RNFLT of the superior quadrant (P<۰.۰۵), whereas for rs۱۹۷۱۰۵۰, a significant association was found with the RNFLT of all four quadrants and average RNFLT (all P<۰.۰۵). However, pairwise comparisons revealed no significant differences between genotypes (P>۰.۰۵ for all pairwise comparisons). The association of rs۱۰۰۳۸۱۷۷ with glaucoma severity was insignificant (P>۰.۰۵), and most patients with the TC genotype (۷۱.۷%) had moderate severity. There was no significant association between rs۱۹۷۱۰۵۰ and glaucoma severity (P>۰.۰۵). Conclusions: We observed genetic links between some, but not all, characteristics of POAG and the rs۱۰۰۳۸۱۷۷ and rs۱۹۷۱۰۵۰ SNPs of WDR۳۶. Follow-up studies on these and other WDR۳۶ SNPs in populations with different genetic backgrounds are necessary to confirm this genetic association. Keywords: glaucomas primary open angle glaucoma WD repeat-containing protein ۳۶ genetic polymorphism single nucleotide polymorphism optical coherence tomography family medical history