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The C677T mutation in methylenetetrahydrofolate reductase gene, plasma homocysteine concentration and the risk 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+ or -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 > or =90 percentile of the control group which was > or =12.4 micro mol/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 micro mol/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 micro mol/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 micro mol/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.

Authors+Show Affiliations

,

1st Department of Coronary Artery Disease, National Institute of Cardiology, Warsaw, Poland.

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Source

Kardiologia polska 59:7 2003 Jul pg 17-26; discussion 26

MeSH

Adult
Aged
Case-Control Studies
Coronary Angiography
Coronary Artery Disease
Cysteine
Female
Folic Acid
Homocysteine
Humans
Hyperhomocysteinemia
Male
Methylenetetrahydrofolate Reductase (NADPH2)
Middle Aged
Multivariate Analysis
Point Mutation
Polymerase Chain Reaction
Polymorphism, Genetic
Risk Factors
Threonine
Vitamin B 12

Pub Type(s)

Journal Article

Language

eng

PubMed ID

14560345

Citation

Kadziela, Jacek, et al. "The C677T Mutation in Methylenetetrahydrofolate Reductase Gene, Plasma Homocysteine Concentration and the Risk of Coronary Artery Disease." Kardiologia Polska, vol. 59, no. 7, 2003, pp. 17-26; discussion 26.
Kadziela J, Janas J, Dzielińska Z, et al. The C677T mutation in methylenetetrahydrofolate reductase gene, plasma homocysteine concentration and the risk of coronary artery disease. Kardiol Pol. 2003;59(7):17-26; discussion 26.
Kadziela, J., Janas, J., Dzielińska, Z., Szperl, M., Gaździk, D., Chotkowska, E., ... Ruzyłło, W. (2003). The C677T mutation in methylenetetrahydrofolate reductase gene, plasma homocysteine concentration and the risk of coronary artery disease. Kardiologia Polska, 59(7), pp. 17-26; discussion 26.
Kadziela J, et al. The C677T Mutation in Methylenetetrahydrofolate Reductase Gene, Plasma Homocysteine Concentration and the Risk of Coronary Artery Disease. Kardiol Pol. 2003;59(7):17-26; discussion 26. PubMed PMID: 14560345.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The C677T mutation in methylenetetrahydrofolate reductase gene, plasma homocysteine concentration and the risk of coronary artery disease. AU - Kadziela,Jacek, AU - Janas,Jadwiga, AU - Dzielińska,Zofia, AU - Szperl,Małgorzata, AU - Gaździk,Danuta, AU - Chotkowska,Ewa, AU - Piotrowski,Walerian, AU - Ruzyłło,Witold, PY - 2003/10/16/pubmed PY - 2004/1/13/medline PY - 2003/10/16/entrez SP - 17-26; discussion 26 JF - Kardiologia polska JO - Kardiol Pol VL - 59 IS - 7 N2 - 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+ or -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 > or =90 percentile of the control group which was > or =12.4 micro mol/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 micro mol/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 micro mol/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 micro mol/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. SN - 0022-9032 UR - https://www.unboundmedicine.com/medline/citation/14560345/The_C677T_mutation_in_methylenetetrahydrofolate_reductase_gene_plasma_homocysteine_concentration_and_the_risk_of_coronary_artery_disease_ L2 - https://medlineplus.gov/coronaryarterydisease.html DB - PRIME DP - Unbound Medicine ER -