Reviews

The role of gene polymorphisms in diabetic retinopathy

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Abstract

Diabetic retinopathy (DR) is the most frequent microvascular complication of diabetes mellitus (DM) and remains a leading cause of preventable blindness in the working-age population. Its course is notoriously variable: some patients with long-standing, poorly controlled diabetes never develop sight-threatening disease, whereas others progress rapidly despite reasonable metabolic control. This clinical heterogeneity, which the traditional risk factors cannot fully explain, has directed attention towards the inherited component of susceptibility. This review summarizes current understanding of the genetic architecture of DR, with particular emphasis on three extensively studied candidate genes: the vascular endothelial growth factor A gene (VEGFA), the angiotensin-converting enzyme gene (ACE) and the apolipoprotein E gene (APOE), specifically their most investigated polymorphisms: VEGFA rs699947, rs2010963 and rs3025039; ACE rs1799752 I/D; and APOE rs429358 and rs7412 (ε2/ε3/ε4). The evidence linking individual polymorphisms to disease is examined alongside the picture emerging from genome-wide association studies (GWAS), and the persistent inconsistency among studies is discussed in the context of ethnic differences, phenotype definition and limited statistical power. Finally, the review considers how genetic insight is beginning to inform therapy, from the established anti-VEGF paradigm to genebased approaches now in clinical trials, and outlines the main obstacles that still separate genetic findings from routine clinical use.

Keywords: candidate gene, gene polymorphism, vascular endothelial growth factor, renin-angiotensin system, genetic predisposition

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