JPH2 is a novel susceptibility gene on chromosome 20q associated with diabetic retinopathy in a Taiwanese population

Abstract

A number of genes on human chromosome 20 have been implicated in susceptibility to diabetic retinopathy (DR) in type 2 diabetes (T2D) patients. This study investigated the association between genetic variants on chromosome 20 and DR development in T2D patients in a Taiwanese population. Unrelated subjects with T2D, without DR (n = 575) and with DR (n = 174), were genotyped for single nucleotide polymorphisms (SNPs) using Illumina BeadChips and genotypes compared between these 2 groups. Seven SNPs on chromosome 20 demonstrated associations with DR, with p-values < 1×10-6. After controlling for diabetic duration and haemoglobin A1C, rs761207 and rs6031415, in junctophilin 2 (JPH2), remained associated to DR and increased the risk for DR development 1.43-fold (95% confidence interval (CI) = 1.04-1.98) and 1.42-fold (95% CI = 1.02-1.97), respectively. These SNPs were also associated with non-proliferative DR. The results implicate that genetic variants of JPH2 are associated with the pathogenesis of DR, particularly in the earlier nonproliferative phase. Given that JPH2 is an essential regulator of calcium flux and that vascular endothelial growth factor, which has previously been implicated in DR, is a mediator of calcium entry, calcium release, and endothelial permeability, our finding indicates that JPH2 is a plausible new candidate gene for DR development.