title: Differing relationships of methylene tetrahydrofolate reductase genotypes with cardiovascular risk in familial and polygenic hypercholesterolaemia.
abstract: BACKGROUND
  Plasma homocysteine and the methylene tetrahydrofolate reductase C677T polymorphism have been suggested as being risk factors for cardiovascular disease.
  
  
  OBJECTIVE
  To determine whether plasma homocysteine and the methylene tetrahydrofolate reductase C677T polymorphism are risk factors for coronary heart disease in patients with heterozygous familial hypercholesterolaemia as compared with those with polygenic hyperlipidaemia.
  
  
  METHODS
  Plasma homocysteine and the methylene tetrahydrofolate reductase polymorphism were assessed with other risk factors in 112 patients with familial hypercholesterolaemia and 72 patients with polygenic hyperlipidaemia, of whom 29 (25.8%) and 30 (41%) respectively had established cardiovascular disease and in 100 healthy normal subjects.
  
  
  RESULTS
  Plasma homocysteine was not significantly elevated in patients with and without coronary heart disease with familial hypercholesterolaemia or polygenic hyperlipidaemia compared with controls. The allele frequencies for C677T were significantly different in patients with coronary heart disease and with polygenic hyperlipidaemia (0.35 versus 0.29) (P = 0.02) as opposed to those with coronary heart disease and familial hypercholesterolaemia (0.25 versus 0.30) (P = 0.63). Methylene tetrahydrofolate reductase genotype but not homocysteine had a weak association with coronary heart disease in logistic regression analysis in patients with polygenic hyperlipidaemia (P = 0.05) but neither methylene tetrahydrofolate reductase genotype or plasma homocysteine was a risk factor in patients with familial hypercholesterolaemia.
  
  
  CONCLUSIONS
  Whilst methylene tetrahydrofolate reductase genotype may be a weak risk factor for coronary heart disease in polygenic hyperlipidaemia as opposed to familial hypercholesterolaemia, homocysteine does not seem to be an important risk factor for coronary heart disease in patients in southern UK.
authors.affiliation: Department of Chemical Pathology, King's College (Guy's, King's and St. Thomas' Medical School), St Thomas' Hospital Campus, London, UK. Anthony.Wierzbicki@kcl.ac.uk
authors.forename: A S
authors.initials: AS
authors.lastname: Wierzbicki
authors.forename: M
authors.initials: M
authors.lastname: Lambert-Hammill
authors.forename: E
authors.initials: E
authors.lastname: Junadi
authors.forename: P J
authors.initials: PJ
authors.lastname: Lumb
authors.forename: M A
authors.initials: MA
authors.lastname: Crook
mesh_terms: D000328:Adult; D000368:Aged; D003327:Coronary Disease / Q000097:blood*; D005260:Female; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood*; D016015:Logistic Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D020412:Multifactorial Inheritance; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D012307:Risk Factors
chemical_list: D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)