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Family-based investigation of the C677T polymorphism of the methylenetetrahydrofolate reductase gene in ischaemic heart disease.

Abstract：

BACKGROUND:Elevated homocysteine is associated with ischaemic heart disease (IHD). The C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene results in reduced MTHFR enzyme activity and reduced methylation of homocysteine to methionine resulting in mild hyperhomocysteinaemia. Case-control association studies of the role of the C677T MTHFR polymorphism in IHD have produced conflicting results. We therefore used newly described family-based association tests to investigate the role of this polymorphism in IHD, in a well-defined population. METHODS:A total of 352 individuals from 129 families (discordant sibships and parent-child trios) were recruited. Linkage disequilibrium between the polymorphism and IHD was tested for using the combined transmission disequilibrium test (TDT)/sib-TDT and pedigree disequilibrium test (PDT). Homocysteine levels were measured. RESULTS:Both the TDT/sib-TDT and PDT analyses found a significantly reduced transmission of the T allele to affected individuals (P=0.016 and P=0.021). There was no significant difference in homocysteine levels between affected and unaffected siblings. TT homozygotes had mean homocysteine levels significantly higher than those of TC heterozygotes (P<0.001) and CC homozygotes (P<0.001). CONCLUSIONS:These data suggest that in contrast to the conventional hypothesis the T allele may be protective against IHD, independent of homocysteine levels.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Spence MS,McGlinchey PG,Patterson CC,Belton C,Murphy G,McMaster D,Fogarty DG,Evans AE,McKeown PP

doi

10.1016/s0021-9150(02)00239-3

keywords:

subject

Has Abstract

pub_date

2002-12-01 00:00:00

pages

293-9

issue

2

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(02)00239-3

journal_volume

165

pub_type

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