HTRA1 Polymorphism in Patients With Proliferative Diabetic Retinopathy in Type 2 Diabetes

Abstract

Purpose:: Diabetic retinopathy is one of the leading causes of blindness in the developed world. The most severe form is proliferative diabetic retinopathy (PDR) characterized by retinal neovascularization, vitreous hemorrhage, and tractional retinal detachment. Recently, a single-nucleotide polymorphism (SNP) in the promoter region of HTRA1 on chromosome 10q36 (rs11200638) was shown to be associated with choroidal neovascularization in wet age-related macular degeneration. Since both diseases involve neovascularization, we reason that HTRA1 may also play a role in PDR.

Methods:: A case-control study was performed. Clinical examination was performed in all participants. 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:: The case group consisted of 151 T2DM patients with PDR and controls were 93 patients who had T2DM for at least 10 years and had no diabetic retinopathy. Individual analysis revealed that the rs11200638 showed an association trend with PDR, although not statistically significant (P<0.2). Post hoc analysis showed that this risk increased additively with the presence of each A allele.

Conclusions:: Allelic variability within the HTRA1 gene at rs11200638 showed a association trend of PDR in patients with T2DM. Genotyping of a second replication cohort is in progress. Our study may provide insight on to whether HTRA1 plays a role in diabetic retinopathy.

Keywords: diabetic retinopathy • genetics • diabetes