SMOKING AS A TRIGGER FACTOR IN THE DEVELOPMENT OF DIABETIC ANGIOPATHY OF LOWER EXTREMITIES IN MEN WITH METHYLENETETRAHYDROFOLATEREDUCTASE 677TT GENOTYPE.
Enhanced thrombogenesis in patients with diabetes mellitus (D) is related to genetically determined disorders of the blood coagulation system analogous to those associated with hereditary thrombophilia. The aim of this work was to elucidate the relationship between the functionally significant methylenetetrahydroxyfolatereductase (MTHFR) C677T (rs1801133) gene polymorphism and the development of diabetic angiopathy of lower extremities (DALE) in ethnic Russian men residing in Central Russia (mostly Kursk region). The study involved 434 subjects including 50 with DALE and 384 healthy volunteers. All of them were genotypedfor the MTHFR C677T gene polimorphim by real-time PCR with allele discrimination using TaqMan-probes. No significant differences in the frequency of alleles of MTHFR C677T gene polymorphism were documented between the general samples and sex-matched groups. Stratified sex-specific analysis showed that 677TT genotype is associated with increased risk of DALE in smoking men (OR 4.2; 95% CI 1.28-13.79, p=0.01). In non-smoking men the 677TTgenotype was unrelated to the development of this complication. It is concluded that the risk of DALE is determined by the close relationship between genetic (UTHFR gene) and exogenous (smoking) factors which suggests the multifactorial nature of this pathology.