Study of Methylene Tetra hydro Folate Reductase Enzyme Single nucleotide polymorphism (C667T) (rs180113) and Susceptibility to Diabetic Septic Foot among Diabetic Sudanese Patients

Abstract

Abstract Background: Diabetic foot ulcer is considered as the most serious diabetes complication; contribute significantly to morbidity and mortality of diabetic patients in Sudan. Globally there are proven genetic based studies in diabetic septic foot predisposition, whereas a few studies have been done in Sudan. Objective: This study was intended to estimate the association of (C667T) SNP (rs180113) in the methylene tetrahydro folate reductase (MTHFR) enzyme with the DSF predisposition, and the role of some non-genetic risk factors in diabetic Sudanese population. Method: A cross-sectional case-control study was conducted, 55 were diabetic septic foot (DSF) patients represent the case group and 75 diabetic patients (DM) without septic complication as control. The (C667T) (rs180113) Polymorphism was detected by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) using Hinf I enzyme. Results: The analysis of age among cases and controls showed that 94.4% of cases are at age group more than 40 years while 76.4% of controls are at this age group, with a high significant difference between DSF and DM ( p – value = 0.005, OR = 0.190, CI = 0.688 – 0.053), no gender difference has been observed between DSF and DM (p – value = 0.510), DSF with a family history of diabetes are 66.7% and 63.4% of DM have a family history, with no significant difference observed between DSF and DM . 16.7% of DSF are alcohol consumers while only 4.2% of DM. DSF are at four times increased risk than those who don’t consume alcohol (p – value = 0.02 , OR = 4.600) . High frequency of neuropathy (58%) was observed among DSF compared to DM , and a high significant association of neuropathy with DSF with a three times increased risk of DSF (p – value = 0.001, OR= 3.452). DSF with retinopathy showed a high significant difference compared to DM with retinopathy (p value = 0.006), with a three times increased risk of DSF (OR = 3.527). Concerning the genotype analysis, the homozygous wild type genotype CC showed high frequency among cases and control with the following percentage (96.7% , 100%) respectively. No significant association between the mutant genotype and DSF predisposition. Conclusion: The results of this study indicates that MTHFR (C667T) (rs180113) polymorphism is not associated with the increased risk of diabetic septic foot among Sudanese diabetic patients, and neuropathy, retinopathy might be a strong pathological cases lead to diabetic septic foot development.