title: 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.
authors.affiliation: Regional Medical Cardiology Centre, Royal Victoria Hospital, Grosvenor Road, BT12 6BA, Belfast, UK.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Spence
authors.forename: Paul G
authors.initials: PG
authors.lastname: McGlinchey
authors.forename: Chris C
authors.initials: CC
authors.lastname: Patterson
authors.forename: Christine
authors.initials: C
authors.lastname: Belton
authors.forename: Gillian
authors.initials: G
authors.lastname: Murphy
authors.forename: Dorothy
authors.initials: D
authors.lastname: McMaster
authors.forename: Damian G
authors.initials: DG
authors.lastname: Fogarty
authors.forename: Alun E
authors.initials: AE
authors.lastname: Evans
authors.forename: Pascal P
authors.initials: PP
authors.lastname: McKeown
mesh_terms: D000328:Adult; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D017202:Myocardial Ischemia / Q000235:genetics* / Q000378:metabolism; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D011110:Polymorphism, Genetic; D012737:Sex Factors
chemical_list: D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)