Genetic causes of mild hyperhomocysteinemia in patients with premature occlusive coronary artery diseases

Elevated plasma homocysteine is increasingly being recognized as a risk factor for coronary artery disease (CAD). Although there is general agreement on the importance of micronutrients and genetic predisposition to elevated plasma homocysteine, the exact influence of the known prevalent mutations i...

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Bibliographic Details
Published in:	Atherosclerosis Vol. 143; no. 1; pp. 163 - 170
Main Authors:	Tsai, Michael Y., Welge, Barry G., Hanson, Naomi Q., Bignell, Michelle K., Vessey, John, Schwichtenberg, Kerry, Yang, Feng, Bullemer, Faye E., Rasmussen, Rhonda, Graham, Kevin J.
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Ireland Ltd 01-03-1999 Elsevier
Subjects:	5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics Age of Onset B vitamins Biological and medical sciences Cardiology. Vascular system Cardiovascular diseases Coronary Disease - blood Coronary Disease - complications Coronary heart disease Cystathionine beta-Synthase - genetics Cystathionine β-synthase Fasting Female Genotype Heart Homocysteine Homocysteine - blood Humans Hyperhomocysteinemia - complications Hyperhomocysteinemia - genetics Male Medical sciences Methionine - administration & dosage Methionine load Methionine synthase Methylenetetrahydrofolate reductase Methylenetetrahydrofolate Reductase (NADPH2) Oxidoreductases Acting on CH-NH Group Donors - genetics Point Mutation Polymorphism, Genetic Methylenetetrahydrofolate reductase Cystathionine β-synthase Methionine synthase Cardiovascular diseases Homocysteine Methionine load B vitamins Human Methylenetetrahydrofolate reductase (NADPH) Gene Enzyme Risk factor Cardiovascular disease Oxidoreductases Mutation Coronary heart disease Genetic determinism Blood plasma
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Summary:	Elevated plasma homocysteine is increasingly being recognized as a risk factor for coronary artery disease (CAD). Although there is general agreement on the importance of micronutrients and genetic predisposition to elevated plasma homocysteine, the exact influence of the known prevalent mutations in genes which regulate homocysteine metabolism is not clear. We studied 376 cases of individuals with premature CAD with respect to their fasting and post-methionine load (PML) total homocysteine (tHcy) concentrations. We also determined the presence or absence of the T 833C and G 919A mutations of the cystathionine- β-synthase (CBS) gene, the C 677T mutation of the methylene tetrahydrofolate reductase (MTHFR) gene, and the A 2756G transition of the B 12 dependent methionine synthase (MS) gene. Our objectives were therefore both to confirm the relationship of plasma homocysteine with premature CAD and to examine the importance of genetic influence on both fasting and PML homocysteine. Approximately 32% of the CAD patients had fasting hyperhomocysteinemia and 16% had PML hyperhomocysteinemia. Of these, 8.5% had both forms of hyperhomocysteinemia (combined hyperhomocysteinemia). The T 833C mutation in the CBS gene and the thermolabile C 677T mutation in the MTHFR gene seem to play an important role in the subset of individuals with combined hyperhomocysteinemia. The A 2756G transition in the MS gene is not associated with elevated plasma tHcy. Many cases (47%) of hyperhomocysteinemia are not associated with micronutrient deficiencies, impaired renal function, and/or currently known genetic mutations. Further work is needed to study whether unknown mutations, particularly those residing in the intronic sequences of the genes involved in homocysteine metabolism, other environmental factors, or interaction of gene, nutrient, and environmental factors may be the cause of currently unexplained cases of mild hyperhomocysteinemia.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0021-9150 1879-1484
DOI:	10.1016/S0021-9150(98)00271-8