Dual mapping of MTHFR C677T (A1298C) and BDNF G196A (Val66Met) polymorphisms in patients with diabetic peripheral neuropathy.

Abstract

Diabetic peripheral neuropathy (DPN) is a loss of distal sensory function in the lower limbs that is accompanied by pain and severe morbidity. The goal of this study was to perform a screening of the MTHFR C677T (A1298C) and BDNF G196A (Val66Met) polymorphisms and determine their possible relationships using biochemical blood tests and clinical presentations of symptoms in Jordanian patients with DPN. A cross-sectional study was conducted, and medical records were used to identify and recruit patients with DPN and collect their demographic and clinical characteristics. The total neuropathy score (TNSr) was used to assess the severity of sensory symptoms. In addition, direct sequencing was performed after Polymerase Chain Reaction (PCR) amplification to screen the two single nucleotide polymorphisms (SNPs) of interest. Ninety patients with DPN participated in the study. The MTHFR-SNP variant (CT) and (TT) genotypes were identified in 39 (43.3%) and 19 (21.1%) patients, respectively. On the other hand, the BDNF-SNP variant (GA) and (AA) genotypes were identified in 22 (24.4%) and 11 (12.2%) patients, respectively. The distributions of the genotype frequencies of the MTHFR-SNP and BDNF-SNP variants statistically differed between patients with DPN and the control group (p < 0.0001, p < 0.002). Moreover, patients carrying variant genotypes of the two analyzed SNPs were more likely to have unsatisfactory HbA1c levels (> 7 mg/dl, p = 0.029) and moderate to severe symptoms (TNSr score 8-24). The results of this study show that the MTHFR C>T-677 SNP and the BDNF G>A-196 SNP can be used as genetic risk markers for DPN. Assessing patients' genetic-metabolic risk profiles is recommended for providing personalized treatment.