HTRA1 Polymorphism in Patients With Proliferative Diabetic Retinopathy in Type 1 Diabetes

Abstract

Purpose:: Proliferative diabetic retinopathy (PDR) is a prevalent morbidity associated with juvenile onset diabetes and is characterized with retinal neovascularization. Recent research demonstrated that a single-nucleotide polymorphism (SNP) in the promotor region of the HTRA1 gene on chromosome 10q36 (rs11200638) increased the risk for developing choroidal neovascularization in wet age-related macular degeneration (AMD). We examined allelic variability at this SNP for association with PDR in patients with juvenile onset diabetes.

Methods:: Using DNA extracted from peripheral blood leukocytes, the specific region of the HTRA1 gene containing the rs11200638 polymorphism was amplified by using site specific primers. rs11200638 allelic scoring was done by RFLP restriction enzyme digestion and gel electrophoresis.

Results:: In 338 patients with PDR, and 374 controls, there was a significant difference between genotypes in patients with and without PDR (p<0.01). Post hoc analysis showed that this risk increased multiplicatively with the presence of each A allele, with an odds ratio of 1.83 (p<0.01, 95% CI 1.45, 2.32).

Conclusions:: Allelic variation within the rs11200638 of HTRA1 is significantly associated with presence of PDR in patients with juvenile onset diabetes. Identification of the underlying pathogenetic mechanism will aid development of new diagnostic and therapeutic methods.

Keywords: diabetic retinopathy • gene/expression • diabetes