Mutations in methylenetetrahydrofolate reductase and in cysthationine beta synthase: is there a link to homocysteine levels in peripheral arterial disease?

Abstract

Peripheral arterial disease (PAD) is an atherosclerotic disturbance characterized by a progressive obstruction of lower limb arteries. Many risk factors associated with PAD development have being reported in the literature. The present study aimed to investigate whether mutations in the methylenetetrahydrofolate reductase (MTHFR) or in the cystathionine beta synthase (CBS) genes are associated with higher levels of homocysteine and the risk of PAD in patients from Brazil. This study analyzed 39 patients with PAD and 32 without PAD in whom risk factors and C677T mutations in the MTHFR gene and both 844ins68 and T833C mutations in the CBS gene were investigated. Although higher levels of homocysteine could be observed in patients with PAD compared to controls, no association between the increase of homocysteine and the frequency of C677T, 844ins68, and T833C mutations could be observed. The results suggest that these mutations do not appear to be related to either homocysteine levels or the development of the disease. However, hyperhomocysteinemia and smoking are important factors in PAD development.

Association of Methylentetraydrofolate Reductase (MTHFR) 677 C > T gene polymorphism and homocysteine levels in psoriasis vulgaris patients from Malaysia: a case-control study

“…The MTHFR gene polymorphism was reported to be associated with hyperhomocysteinaemia which has deleterious effects on the cardiovascular system [13,28]. Hence, psoriasis vulgaris patients with MTHFR gene polymorphism may be at greater risk of cardiovascular diseases and thromboembolic events.…”

“…The enzymatic remethylations of homocysteine to methionine by 5-methyltetrahydrofolate homocysteine methyltransferase rely heavily on the adequate levels of vitamin B 12 and folic acid. Therefore, the deficiencies of the Vitamin B 12 and folic acid will lead to hyperhomocysteinaemia and hypomethioninaemia [13-16]. …”

The role of nutrition and body composition in peripheral arterial disease

“…28,30,37,40,41,43–48 Six studies showed no significant difference in mutation prevalence between patients with PAD and healthy controls. 37,40,42,43,45,46 However, two studies showed a higher prevalence of the MTHFR 667T allele or TT genotype in patients with PAD than in individuals without cardiovascular disease. 41,44 The results of two meta-analysis were also conflicting.…”

Studying the association between methylenetetrahydrofolate reductase (MTHFR) 677 gene polymorphism, cardiovascular risk and lichen planus

“…One of the major determinants of Hcy levels is the folic acid (folate). Accordingly, folate deficiency as well as MTHFR gene polymorphism can affect plasma Hcy levels causing hyperhomocysteinemia . Frosst et al demonstrated the association of the homozygous mutant genotype (677TT) with mild hyperhomocysteinemia.…”

“…Accordingly, folate deficiency as well as MTHFR gene polymorphism can affect plasma Hcy levels causing hyperhomocysteinemia. 7 Frosst et al 8 demonstrated the association of the homozygous mutant genotype (677TT) with mild hyperhomocysteinemia. Then, it became evident that this relationship was found only in individuals with folate deficiency.…”