Vol 59, No 7 (2003)
Other
Published online: 2005-12-12
Submitted: 2012-12-28
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The C677T mutation in methylenetetrahydrofolate reductase gene, plasma homocysteine concentration and the risk of coronary artery disease

Jacek Kądziela, Jadwiga Janas, Zofia Dzielińska, Małgorzata Szperl, Danuta Gaździk, Ewa Chotkowska, Walerian Piotrowski, Witold Rużyłło
Kardiol Pol 2003;59(7):22-25.
Vol 59, No 7 (2003)
Other
Published online: 2005-12-12
Submitted: 2012-12-28

Abstract

Background: The C677T mutation in methylenetetrahydrofolate reductase (MTHFR) gene is one of the causes of an elevated homocysteine plasma concentration and is probably one of the atherosclerotic risk factors.
Aim: To assess the relationship between the presence of the MTHFR gene mutation, plasma homocysteine concentration and the risk of coronary artery disease (CAD).
Methods: The study group consisted of 120 consecutive patients (78% were male, mean age 59.2±9.6 years) with angiographically confirmed CAD and 106 healthy volunteers (76% were male, mean age 47.4±6.0 years). The MTHFR gene mutation was detected based on the polymerase chain reaction and digestion with restrictive endonuclease HinfI. Total homocysteine plasma concentration was measured using HPLC. Folic acid and vitamin B12 plasma levels were assessed using the chemiluminescence method. Hyperhomocysteinemia was defined as homocysteine concentration ≥90 percentile of the control group which was ≥12.4 µmol/L.
Results: The incidence of the mutation of allele T and the genotype TT was similar in patients and controls (51.7% vs 56.6%, and 9.2% vs 10.4%, NS, respectively). The folic acid and vitamin B12 levels were not related to the MTHFR genotype (folic acid: 8.1 ng/L in homozygotes TT vs 8.6 in heterozygotes CT and 8.3 in homozygotes CC; and vitamin B12: 273 pg/L vs 303.3 vs 314.3, respectively). Although homozygotes TT had significantly higher homocysteine concentration than heterozygotes and homozygotes CT or CC (15.4 vs 11.0 vs 11.2 µmol/L, p<0.001), the odds ratio for CAD in genotype TT was 0.87 (95% CI 0.5-2.1, NS). The odds ratio in subjects with at least one mutated T allele was 0.82 (95%CI 0.5-1.4, NS). Homocysteine plasma concentration was significantly higher in patients with CAD than controls (12.8±5.1 vs 10.0±5.0 µmol/L, p<0.001) and correlated significantly with folic acid (r= -0.28, p=0.0001), vitamin B12 (r= -0.19, p<0.005), age (r=0.35, p=0.0001) and creatinine (r=0.26, p=0.0001). The odds ratio for CAD in subjects with hyperhomocysteinemia was 7.1 (95%CI 3.4-14.9, p=0.001) and was 2.6 (95%CI 1.6-4.1, p=0.0001) with a homocysteine increase of 5 µmol/L. Multivariate analysis showed that hyperhomocysteinemia was an independent risk factor of CAD (OR 2.7, 95%CI 1-7.2, p<0.05).
Conclusions: Hyperhomocysteinemia rather than a mutation in the methylenetetrahydrofolate reductase gene, is an independent risk factor of coronary artery disease.

Abstract

Background: The C677T mutation in methylenetetrahydrofolate reductase (MTHFR) gene is one of the causes of an elevated homocysteine plasma concentration and is probably one of the atherosclerotic risk factors.
Aim: To assess the relationship between the presence of the MTHFR gene mutation, plasma homocysteine concentration and the risk of coronary artery disease (CAD).
Methods: The study group consisted of 120 consecutive patients (78% were male, mean age 59.2±9.6 years) with angiographically confirmed CAD and 106 healthy volunteers (76% were male, mean age 47.4±6.0 years). The MTHFR gene mutation was detected based on the polymerase chain reaction and digestion with restrictive endonuclease HinfI. Total homocysteine plasma concentration was measured using HPLC. Folic acid and vitamin B12 plasma levels were assessed using the chemiluminescence method. Hyperhomocysteinemia was defined as homocysteine concentration ≥90 percentile of the control group which was ≥12.4 µmol/L.
Results: The incidence of the mutation of allele T and the genotype TT was similar in patients and controls (51.7% vs 56.6%, and 9.2% vs 10.4%, NS, respectively). The folic acid and vitamin B12 levels were not related to the MTHFR genotype (folic acid: 8.1 ng/L in homozygotes TT vs 8.6 in heterozygotes CT and 8.3 in homozygotes CC; and vitamin B12: 273 pg/L vs 303.3 vs 314.3, respectively). Although homozygotes TT had significantly higher homocysteine concentration than heterozygotes and homozygotes CT or CC (15.4 vs 11.0 vs 11.2 µmol/L, p<0.001), the odds ratio for CAD in genotype TT was 0.87 (95% CI 0.5-2.1, NS). The odds ratio in subjects with at least one mutated T allele was 0.82 (95%CI 0.5-1.4, NS). Homocysteine plasma concentration was significantly higher in patients with CAD than controls (12.8±5.1 vs 10.0±5.0 µmol/L, p<0.001) and correlated significantly with folic acid (r= -0.28, p=0.0001), vitamin B12 (r= -0.19, p<0.005), age (r=0.35, p=0.0001) and creatinine (r=0.26, p=0.0001). The odds ratio for CAD in subjects with hyperhomocysteinemia was 7.1 (95%CI 3.4-14.9, p=0.001) and was 2.6 (95%CI 1.6-4.1, p=0.0001) with a homocysteine increase of 5 µmol/L. Multivariate analysis showed that hyperhomocysteinemia was an independent risk factor of CAD (OR 2.7, 95%CI 1-7.2, p<0.05).
Conclusions: Hyperhomocysteinemia rather than a mutation in the methylenetetrahydrofolate reductase gene, is an independent risk factor of coronary artery disease.
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Keywords

methylenetetrahydrofolate reductase gene - homocysteine - folic acid - coronary artery disease - atherosclerosis

About this article
Title

The C677T mutation in methylenetetrahydrofolate reductase gene, plasma homocysteine concentration and the risk of coronary artery disease

Journal

Kardiologia Polska (Polish Heart Journal)

Issue

Vol 59, No 7 (2003)

Pages

22-25

Published online

2005-12-12

Bibliographic record

Kardiol Pol 2003;59(7):22-25.

Keywords

methylenetetrahydrofolate reductase gene - homocysteine - folic acid - coronary artery disease - atherosclerosis

Authors

Jacek Kądziela
Jadwiga Janas
Zofia Dzielińska
Małgorzata Szperl
Danuta Gaździk
Ewa Chotkowska
Walerian Piotrowski
Witold Rużyłło

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