Peripheral arterial disease and methylenetetrahydrofolate reductase (MTHFR) C677T mutations: A case-control study and meta-analysis

Abstract

We have found a strong association between raised homocysteine, the TT genotype, and PAD.

ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing

“…20 The potential associations between MTHFR genotype status and a number of medical complications have been evaluated using methodologies such as case-control, cohort, Mendelian randomization, and meta-analysis. A modest positive association has been found between the MTHFR "thermolabile" polymorphism and many different medical complications, including, but not limited to, thromboembolic disease (in non-North-American populations only), 21,22 stroke, [23][24][25][26][27] aneurysm, 28 peripheral artery disease, 29 migraine, 30 hypertension, 31,32 recurrent pregnancy loss, 33,34 male infertility, 35,36 risk for offspring with neural tube defects, 37,38 certain cancers, [39][40][41] neuropsychiatric disease, 42 and chemotherapy toxicity. 43,44 …”

Pathophysiology of Abdominal Aortic Aneurysm – Genetic Factors and Homocysteine Metabolism

“…The homozygous and heterozygous genotypes (CT) and (TT) have been shown to be associated with raised Hcy levels and lower MTHFR enzyme concentrations. In one study there was a 36% difference in mean Hcy levels between wildtype and TT genotypes (Khandanpour et al, 2009), while a 47% difference was demonstrated in another study (Rassoul et al, 2000). Further to this, a strong association has been demonstrated between the TT genotype, hyperHcy and coronary, cerebro and peripheral atherosclerotic disease (Khandanpour et al, 2009;Klerk et al, 2002;Moat et al, 2004).…”

“…In one study there was a 36% difference in mean Hcy levels between wildtype and TT genotypes (Khandanpour et al, 2009), while a 47% difference was demonstrated in another study (Rassoul et al, 2000). Further to this, a strong association has been demonstrated between the TT genotype, hyperHcy and coronary, cerebro and peripheral atherosclerotic disease (Khandanpour et al, 2009;Klerk et al, 2002;Moat et al, 2004). Significantly, the association of the MTHFR genotype with Hcy levels is only observed when concomitant inadequate folate concentrations are present (Guilliams, 2004;Castro et al, 2006), although low folate levels independent of MTHFR have not been shown to cause hyperHcy (Spark et al, 2003).…”

“…Currently, 33 MTHFR gene mutations have been reported as causing severe hyperHcy. Perhaps more clinically relevant to aneurysmal disease is a polymorphism in the MTHFR gene at the 677 locus which involves substitution of a cytosine nucleotide for a thymine (Strauss et al, 2003;Jones et al, 2005;Khandanpour et al, 2009;Sunder-Plassman & Fodinger, 2003;Klerk et al, 2002). It is subsequently referred to as the T-allele.…”

Prevalence of thrombophilic mutations in male patients with peripheral arterial disease

“…Kafkas ırkında homozigot MTHFR C677T mutasyonunun sıklığı %5-% 20 arasında değişmektedir (25). Dokuz ayrı çalışmayı kapsayan bir meta-analizde MTHFR C677T alelinin artmış PAH riskiyle ilişkili olduğu gösterilmiştir (26). Aksine, başka bir çalışmada MTHFR C677T polimorfizminin PAH için bir risk faktörü olmadığı bildirilmiştir (11).…”