MTHFR 677C>T (rs1801133) variant is associated with homocysteinemia but not with clinical severity in patients with peripheral arterial occlusive disease

Abstract Peripheral arterial occlusive disease (PAOD) is characterized by atherosclerotic lesions involving non-cardiac and non-cerebral arteries and disturbances in the axial vessels and at the microcirculatory level, which may lead to critical ischemia of lower limbs. Conflicting results have been reported about the role of the MTHFR 677 C > G (rs1801133) variant on the susceptibility to PAOD. The aim was to evaluate the association between the MTHFR 677C > T variant with susceptibility and severity of PAOD and with serum levels of homocysteine (Hcy). A case-control study enrolled 157 patients with PAOD and unrelated 113 controls from Southern Brazil. The clinical severity of the PAOD was assessed by Fontaine classification and anatomoradiological categories by Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC). The MTHFR 677C > T was genotyped using real-time polymerase chain reaction and Hcy levels were determined using chemiluminescence in microparticles assay. The PAOD patients showed higher Hcy than controls but the values did not differ according to Fontaine and TASC categories. The MTHFR 677C > T variant was not associated with PAOD, the clinical stage, and the anatomoradiological categories. However, patients carrying the TT genotype (recessive model) or CT + TT genotypes (dominant model) presented higher levels of Hcy than those carrying other genotypes. In conclusion, the T allele of MTHFR 677C > T variant was associated with hyperhomocysteinemia in PAOD patients, but not in controls. Our data suggested a possible interaction between MTHFR 677C > T variant and the presence of other genetic, epigenetic and environment factors associated with PAOD on modulation of the Hcy metabolism.