Common polymorphisms in MIR146a, MIR128a and MIR27a genes contribute to neuropathy susceptibility in type 2 diabetes.

Abstract Diabetic polyneuropathy (DPN) and cardiovascular autonomic neuropathy (CAN) are common type 2 diabetes complications with a large inter-individual variability in terms of clinical manifestations and severity. Our aim was to evaluate a possible involvement of genetic polymorphisms in miRNA regions in the susceptibility to DPN and CAN. Nine polymorphisms in miRNA genes were studied in a sample of 132 type 2 diabetes patients (T2D) analysed for DPN and 128 T2D patients analysed for CAN. A genotype–phenotype correlation analysis was performed. The T allele of rs11888095 single nucleotide polymorphism (SNP) in MIR128a was significantly associated with a higher risk (ORadj = 4.89, Padj = 0.02), whereas the C allele of rs2910164 SNP in MIR146a was associated with a lower risk to develop DPN (ORadj = 0.49, Padj = 0.09), respectively. A multivariate logistic regression analysis confirmed that both SNPs contribute to DPN (p\0.001 and p = 0.01 for MIR128a and MIR146a, respectively). MIR128a SNP significantly contributed also to DPN score (p = 0.026). Rs895819 SNP in MIR27a was significantly associated with a higher risk to develop early CAN (Padj = 0.023 and ORadj = 3.43). The rs2910164 SNP in MIR146a showed a protective effect respect to early CAN (Padj = 0.052, ORadj = 0.32) and to confirmed CAN (Padj = 0.041, ORadj = 0.13). The same SNP resulted significantly associated with a lower CAN score and a higher E/I (p = 0.002 and p = 0.003, respectively). In conclusion, we described associations of MIR128a and MIR146a SNPs with DPN susceptibility and of MIR146a and MIR27a SNPs with CAN susceptibility. This is the first study showing that genetic variability in miRNA genes could be involved in diabetic neuropathies susceptibility.