Homocysteine,MTHFR gene polymorphisms, and cardio-cerebrovascular risk

Abstract

Vascular diseases are commonly associated with traditional risk factors, but in the last decade scientific evidence has suggested that elevated plasma levels of homocysteine are associated with an increased risk of atherosclerosis and cardiovascular ischaemic events. Cardio- and cerebrovascular diseases are multifactorial, as their aetiopathogenesis is determined by genetic and environmental factors and by gene-gene and gene-environment interactions. Experimental studies have shown that many possible mechanisms are implicated in the pro-atherogenic effect of homocysteine. Hyperhomocysteinaemia may confer a mild risk alone, but it increases the risk of disease in association with other factors promoting vascular lesions. Variants in genes encoding enzymes involved in homocysteine metabolism, or depletion of important cofactors or substrates for those enzymes, including folate, vitamin B12 and vitamin B6, may result in elevated plasma homocysteine levels. Several studies have been performed to elucidate the genetic determinant of hyperhomocysteinaemia in patients with vascular disease, and the MTHFR 677C>T polymorphism is the one most extensively investigated. However, the lack of homogeneity in the data and the high number of factors influencing plasma homocysteine concentrations remain conflicting. Moreover, studies on the evaluation of therapeutic interventions in improving the atherogenic profile, lowering plasma homocysteine levels, and preventing vascular events, have shown inconsistent results, which are reviewed in this paper. More prospective, double-blind, randomized studies, including folate and vitamin B interventions, and genotyping for polymorphisms in genes involved in homocysteine metabolism, might better define the relationship between mild hyperhomocysteinaemia and vascular damage.

The MTHFR C677T Polymorphism and Risk of Acute Lymphoblastic Leukemia: an Updated Meta-analysis Based on 37 Case-control Studies

“…The TT genotype of C677T polymorphism in MTHFR gene was associated with elevated plasma homocysteine level, increased risk of arterial stiffness (Trabetti 2008). Women with elevated total homocysteine concentrations showed a significant association with defective chorionic villous vascularization (Nelen et al, 2000).…”

Methylenetetrahydrofolate Reductase C677T Polymorphism and Recurrent Pregnancy Loss Risk in Asian Population: A Meta-analysis

“…1 Flow chart shows study selection procedure. Twenty-five case-control studies were included in present meta-analysis was associated with elevated plasma homocysteine level, increased risk of arterial stiffness [58] and women with elevated total homocysteine concentrations showed a significant association with defective chorionic villous vascularization [59][60][61]. In embryonic development during pregnancy, the embryo survives and grows by stimulating its own blood supply through angiogenesis.…”

Case report. Role of the Methylene Tetrahydrofolate Reductase (MTHFR) Gene Mutation in Acute Myocardial Infarction

“…It has been shown that the clinical evolution of arterial or venous thrombotic events in patients with MTHFR gene mutation and increased homocysteine levels improves under supplementation with folic acid, as seen also in this case report. 10 Gene disorders that affect clotting factor V, prothrombin, and homocysteine, increase the risk of developing acute coronary syndromes or stroke, especially at a young age. 11 Nevertheless, the screening protocol applies to a relatively low number of subjects, since the number of …”