Association between a MIR499A polymorphism and diabetic neuropathy in type 2 diabetes

Aims: Diabetic polyneuropathy (DPN) and cardiovascular autonomic neuropathy (CAN) affect a large percentage of diabetic people and impact severely on quality of life. As it seems that miRNAs and their variations might play a role in these complications, we investigated whether the rs3746444 SNP in the MIR499A gene could be associated with susceptibility to DPN and/or CAN. Methods: We analyzed 150 participants with type 2 diabetes. DNA was extracted from peripheral blood samples and genotyping was performed by TaqMan genotyping assay. Cardiovascular tests, MNSI-Q and MDNS for neuropathic symptoms and signs, VPT, and thermal thresholds were used for CAN and DPN assessment. We performed a genotype-phenotype correlation analysis. Results: We observed that the GG genotype was associated with a higher risk of developing CAN (P = 0.002 and OR = 16.08, P = 0.0005 and OR = 35.02, for early and confirmed CAN, respectively) and DPN (P = 0.037 and OR = 6.56), after correction for BMI, sex, age, HbA1c and disease duration. Moreover, the GG genotype was associated with worse values of MDNS (P = 0.017), VPT (P = 0.01), thermal thresholds (P = 0.01), and CAN score (P < 0.001). A logistic multivariate analysis confirmed that MIR499A GG genotype, disease duration and HbA1c contributed to early CAN (R-2 = 0.26), while the same variables and age contributed to DPN (R-2 = 0.21). With a multiple linear regression, we observed that GG genotype (P = 0.001) and disease duration (P = 0.035) were the main variables contributing to the CAN score (R2 = 0.35). Conclusions: We described for the first time that the MIR499A genetic variation could be involved in diabetic neuropathies susceptibility. In particular, patients carrying the rs3746444 GG genotype had a higher risk of CAN development, together with a more severe form of CAN. (C) 2017 Published by Elsevier Inc.