Single locus and haplotype association of ENPP1 gene variants with the development of retinopathy among type 2 diabetic patients.

Purpose: The present study was designed to investigate the associations of ENPP1 variants (rs997509, rs1799774, rs1044498 (K121Q), and rs7754561) with diabetic retinopathy (DR) derived from type 2 diabetes mellitus (T2DM).

Methods: Total 501 T2DM patients with and without DR were studied as the case and control group, respectively. All four variants were genotyped by TaqMan assay. Statistical analyses were performed through SNPAlyze and SPSS software.

Results: The statistical analysis of clinical characteristics represented significant differences of HbA1c, and fasting blood sugar between two study groups. The results indicated that among four studied variants, rs997509 and rs7754561 were significantly associated with DR under recessive (P = 0.01) and dominant (P = 0.01) models of inheritance, respectively. One haplotype (T-A-T-A) with a frequency higher than 0.05 was associated with the increased risk of DR (P = 0.04). Genotype-phenotype sub-analysis of rs997509 and rs7754561 showed that only rs7754561 had significant associations with systolic and diastolic blood pressures (P = 0.03 and P = 0.01, respectively); more specifically, A allele carriers of rs7754561 were in a higher risk of blood pressures.

Conclusions: This study suggested that rs997509 and rs7754561 were associated with the increased risk of DR among Iranians with T2DM and rs7754561 might be a potential genetic marker for prognosis and diagnosis of DR.