Association of the PLEKHO2 and PLEKHH1 gene polymorphisms with type 2 diabetic retinopathy in a Taiwanese population

Abstract

Diabetic retinopathy (DR) is a chronic retinal disorder, in which the retinal microvasculature is gradually altered, ultimately leading to blindness. Previous observations on clinical variations of the onset and severity of DR in various patients and populations suggest that genetic polymorphisms contribute to DR development. The present study was undertaken in an attempt to uncover new genetic factors contributing to the development of DR in a Taiwanese population. A well-defined Taiwanese population comprising persons with type 2 diabetes mellitus (T2DM) (n = 749) was recruited for this study. We conducted a genome-wide association study in an independent set of 174 patients with DR and 575 without DR, using Illumina HumanHap550-Duo BeadChip. Eleven single nucleotide polymorphisms (SNPs) with the most significant test statistics (p 1 × 10 −5 ) were selected from one of the models. Of the selected SNPs, rs832882 (G/A) (p = 2.29 × 10 −6 ; odds ratio (OR) = 1.49; 95% confidence interval (CI) = 1.11-2.00) and rs3742872 (G/A) (P = 1.19 × 10 −15 ; OR = 1.95; 95% CI = 1.02-3.72), both identified as having the most significant association with DR, are located in the intronic region of the gene encoding the pleckstrin homology (PH) domain-containing proteins family O member 2 (PLEKHO2) and family H member 1 (PLEKHH1), respectively. Functional prediction analysis strengthened the likelihood of participation of PLEKHO2 and PLEKHH1 in the development of DR. The current findings suggest that the rs832882 and rs3742872 polymorphisms may be harbouring retinopathy susceptibility in a Taiwanese population, and implicate the pathological role of PH domain-containing proteins in DR development.