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The common `thermolabile' variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia

Harmon, DL, Woodside, JV, Yarnell, JWG, McMaster, D, Young, IS, McCrum, EE, Gey, KF, Whitehead, AS and Evans, AE (1996) The common `thermolabile' variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia. QJM-MONTHLY JOURNAL OF THE ASSOCIATION OF PHYSICIANS, 89 (8). pp. 571-577. [Journal article]

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Mild hyperhomocysteinaemia is a major risk factor for vascular disease and neural tube defects (NTDs), conferring an approximately three-fold relative risk for each condition. It has several possible causes: heterozygosity for rare loss of function mutations in the genes for 5,10-methylene tetrahydrofolate reductase (MTHFR) or cystathionine-beta-synthase (CBS); dietary insufficiency of vitamin co-factors B6, B12 or folates; or homozygosity for a common `thermolabile' mutation in the MTHFR gene which has also been associated with vascular disease and NTDs. We quantified the contribution of the thermolabile mutation to the hyperhomocysteinaemic phenotype in a working male population (625 individuals). Serum folate and vitamin B12 concentrations were also measured and their relationship with homocysteine status and MTHFR genotype assessed. The homozygous thermolabile genotype occurred in 48.4, 35.5, and 23.4% of the top 5, 10, and 20% of individuals (respectively) ranked by plasma homocysteine levels, compared with a frequency of 11.5% in the study population as a whole, establishing that the mutation is a major determinant of homocysteine levels at the upper end of the range. Serum folate concentrations also varied with genotype, being lowest in thermolabile homozygotes. The MTHFR thermolabile genotype should be considered when population studies are designed to determine the effective homocysteine-lowering dose of dietary folate supplements, and when prophylactic doses of folate are recommended for individuals.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Research Institutes and Groups:Institute of Nursing and Health Research
Institute of Nursing and Health Research > Centre for Maternal, Fetal and Infant Research
ID Code:7396
Deposited By: Ms Evie Gardner
Deposited On:27 Jan 2010 15:51
Last Modified:18 Oct 2011 14:31

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