Identification of Risk Alleles in the Erythropoietin gene for Proliferative Diabetic Retinopathy in Type I and Type II Diabetics

Abstract

Purpose: Genetic markers for the expression of the glycoprotein erythropoietin (EPO) - a potent promoter of angiogenesis with implications in diabetic microvascular proliferation - have been identified. These markers, or SNPs, can manifest as either risk or protective factors in relation to the development of proliferative diabetic retinopathy (PDR). In this study we are seeking to investigate the prevalence of EPO in pre-retinopathic diabetics of a Brazilian population cohort.

Methods: We evaluated a total of 70 participants, neither of which had developed PDR. The population consisted of 27 type 2 diabetics, 15 type 1 diabetics and an age matched control group of 28 subjects. Participants were genotyped for 3 specific SNPs - locations rs1617640, rs507392, and rs551238 - which have been found to be associated with EPO expression, with the latter two SNPs as part of a disease haplotype (TTA or GCC). The blood samples were collected and the PCR for each SNP was performed after DNA extraction. The PCR products were directly sequenced.

Results: Of the 70 individuals, controls and diabetics, that were genotyped, 39 were homozygous for the T allele (57%) at the location rs1617640, while only a small portion (N=7) were homozygous for the aforementioned protective G allele (10%). The remaining individuals (32%) were heterozygous (TG) (N=23). Within the diabetic population subset (N=42), 24 patients were homozygous for the T allele (60%). From 33 participants evaluated for the disease haplotypes, 20 patients and 9 control subjects were TTA and the GCC haplotype was present in only 1 patient and 3 controls subjects.

Conclusions: These results suggest a majority of individuals are carriers of the EPO16 risk allele and the haplotype TTA described in the literature. The correlation of these data with the patient visual function can provide additional valuable tools for early detection and clinical management of patients more susceptible to diabetic visual damage.

Keywords: 499 diabetic retinopathy • 539 genetics