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

• Published in: Journal of vascular surgery 2009-03, Vol.49 (3), p.711-718
• Main Authors: Khandanpour, Nader, MD, Willis, Gavin, PhD, Meyer, Felicity J., FRCS, Armon, Matthew P., FRCS, Loke, Yoon K., MD, Wright, Anthony J.A, Finglas, Paul M., BSc, Jennings, Barbara A., PhD
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Case-Control Studies; Cross-Sectional Studies; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; England - epidemiology; Female; Gene Frequency; Genetic Predisposition to Disease; Homocysteine - blood; Homozygote; Humans; Hyperhomocysteinemia - complications; Hyperhomocysteinemia - enzymology; Hyperhomocysteinemia - genetics; Male; Medical sciences; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Middle Aged; Multicenter Studies as Topic; Mutation; Odds Ratio; Peripheral Vascular Diseases - enzymology; Peripheral Vascular Diseases - genetics; Phenotype; Polymorphism, Genetic; Randomized Controlled Trials as Topic; Risk Assessment; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels
• ISSN: 0741-5214; 1097-6809
• DOI: 10.1016/j.jvs.2008.10.004

Objective Hyperhomocysteinaemia is associated with peripheral arterial disease (PAD). There are inter-individual variations in the metabolism of homocysteine because of genetic polymorphisms. This study analyzed the role of one polymorphism that is associated with raised homocysteine, as a risk factor for PAD. Methods This study considered the association of methylenetetrahydrofolate reductase ( MTHFR ) C677T polymorphisms with the incidence of PAD by performing a case-control study and a cross sectional study of homocysteine levels. We recruited 133 patients with PAD in Norfolk and compared the MTHFR allele distribution with 457 healthy individuals. We also carried out a meta-analysis to place our data within the context of other published studies. We searched Medline, Embase, and Cochrane databases up to March 2008 for any studies on the association between MTHFR C677T polymorphism and PAD. Results The MTHFR C677T allele frequencies in the cases and controls were 0.37 and 0.33, and the odds ratios for the association of the 677 T allele or TT genotype with PAD were 1.18 (95% Confidence Interval [CI] 0.89, 1.58) and 1.99 (95% CI 1.09, 3.63). Homozygotes for the MTHFR C677T mutation had higher concentrations of plasma total homocysteine, odds ratio 2.82 (95% CI 1.03, 7.77) compared to homozygotes for the MTHFR 677 CC genotype. Twelve of 72 articles retrieved from the database search reported the prevalence of mutations in PAD patients. A meta-analysis of 9 appropriate studies, including our own, showed that being homozygous for the C677T allele was associated with an increased risk of PAD, pooled odds ratio 1.36 (95% CI 1.09, 1.68). Conclusion We have found a strong association between raised homocysteine, the TT genotype, and PAD.