title: Serum homocysteine, methylenetetrahydrofolate reductase gene polymorphism and cardiovascular disease in heterozygous familial hypercholesterolemia.
abstract: Mild hyperhomocysteinemia is considered an important risk factor for vascular disease. A common polymorphism (677C-->T) in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with a decreased enzyme activity and consequent higher circulating levels of homocysteine. We hypothesized that the serum levels of homocysteine and/or the MTHFR polymorphism could influence the risk for coronary artery disease (CAD) in patients with heterozygous familial hypercholesterolemia (FH), who are genetically prone to atherosclerosis. We determined the MTHFR genotype and fasting total serum homocysteine level in 249 adult patients (103 males and 146 females) with heterozygous FH. MTHFR polymorphism was a major determinant of serum homocysteine in adult FH of both sexes. The logistic regression analysis showed that in FH patients a high level of homocysteine (> 12 micromol/l, corresponding to the upper quartile of serum distribution) was the most significant predictor of CAD (n=99) in all the groups considered (all CAD, previous myocardial infarction, myocardial infarction plus angiographically confirmed CAD). The adjusted odds ratio (OR (95% CI)) for the homocysteine-associated risk of CAD (upper quartile versus lower quartiles) was 3.27 (1.60-6.62) in males and females considered together, 5.67 (1.50-21.3) in males and 2.78 (1.17-6.62) in females. LDL cholesterol (upper quartile versus lower quartiles) and hypertension were the other variables independently associated with CAD. In both sexes MTHFR polymorphism was not an independent predictor of CAD. Plasma concentration of serum homocysteine, but not MTHFR genotype, is associated with an increased risk of CAD in male and female patients with heterozygous FH.
authors.affiliation: Department of Internal Medicine, University of Genoa, Viale Benedetto XV 6, 16132 Genoa, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Pisciotta
authors.forename: Claudio
authors.initials: C
authors.lastname: Cortese
authors.forename: Agostino
authors.initials: A
authors.lastname: Gnasso
authors.forename: Laura
authors.initials: L
authors.lastname: Liberatoscioli
authors.forename: Anna
authors.initials: A
authors.lastname: Pastore
authors.forename: Liliana
authors.initials: L
authors.lastname: Mannucci
authors.forename: Concetta
authors.initials: C
authors.lastname: Irace
authors.forename: Giorgio
authors.initials: G
authors.lastname: Federici
authors.forename: Stefano
authors.initials: S
authors.lastname: Bertolini
mesh_terms: D000328:Adult; D000368:Aged; D003324:Coronary Artery Disease / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000494:pharmacology; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)