Methylenetetrahydrofolate reductase gene polymorphism in type 1 diabetes mellitus: Relationship to microvascular complications

Abstract

In patients with type-I diabetes mellitus folate deficiency is associated with endothelial dysfunction. So, polymorphism in genes involved in folate metabolism may have a role in vascular disease. This study was designed to evaluate the relationship between methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and microvascular complications in adolescents with type I diabetes mellitus. A total of 99 patients with disease duration of more than 5 years aged 11–18 years participated in the study. History taking, physical, neurological and fundus examinations were performed. Laboratory investigations included mean glycated hemoglobin in the last year, urinary albumin excretion, serum creatinine, nerve conduction velocity and MTHFR genotype determination. Results revealed that 54 (54.5%) of our patients had normal MTHFR genotype (C/C subgroup), 36 (36.4%) had heterozygous MTHFR gene polymorphism (C/T subgroup) and 9 (9.1%) had homozygous MTHFR gene polymorphism (T/T subgroup). No significant difference was found between the three studied groups as regards age, disease duration or glycemic control. When testing for microalbuminuria, the T/T subgroup showed a significantly higher number of patients with microalbuminuria when compared with C/C and C/T subgroups. Regarding fundus changes, the C/C subgroup showed a significantly lower number of patients with fundus changes when compared with C/T and T/T subgroups .On the other hand the T/T subgroup showed a significantly higher number of patients with fundus changes when compared with the C/T subgroup. For nerve conduction abnormalities, the T/T subgroup showed a significantly higher number of patients with nerve conduction abnormalities when compared with C/C and C/T subgroups. Multivariate forward stepwise logistic regression analysis for determination of independent risk factors that best predicts the occurrence of microalbuminuria, fundus changes and nerve conduction abnormalities revealed MTHFR gene polymorphism to be the most important variable. MTHFR gene polymorphism (T/T) subtype is an important risk factor for the development of micro-vascular complications in patients with type I diabetes mellitus.

Keywords: Methylenetetrahydrofolate reductase gene polymorphism; Microvascular complications; Type 1 diabetes; Microalbuminuria