Homocysteine and the MTHFR 677C -> T allele in premature coronary artery disease. Case control and family studies

Background The aim of this work was to evaluate the role of homocysteine, a nd the MTHFR 677C-->T allele as risk factors for premature coronary artery disease and to analyse the inheritance of this metabolic disorder. Material and methods Case-control and family studies were performed in a sa mple of 76 male patients (age < 55), 95 age-matched controls and 89 patient s' offspring. Plasma total homocysteine concentrations, its nutritional det erminants and the frequency of the MTHFR 677C-->T allele were measured, in addition to conventional risk factors. Results Mild hyperhomocysteinemia (above the 90th percentile of the control group) was seen in 22.4% of patients (P = 0.02) and was an independent pre dictor of premature coronary artery disease (odds ratio of 3.2). The freque ncies of the 677T allele in patients and controls were 0.37 and 0.36 and th ose of the TT genotype were 0.15 and 0.14, respectively. Homozygosity for t he 677T allele was associated with significantly higher homocysteine values (P < 0.00001). Among TT patients, 64% had mild hyperhomocysteinemia, as co mpared to 23% of TT controls. Mild hyperhomocysteinemia showed a strong her editary component, as 36% of patients' offspring had homocysteine levels ab ove the age-adjusted 90th percentile compared to only 13% of patients' spou ses. Among children with the TT genotype, the proportion raised to 83% (P < 0.001). Conclusion In this Spanish population, mild hyperhomocysteinemia is associa ted with the risk of premature coronary artery disease and is highly preval ent in offspring of patients with this condition. The MTHFR TT genotype is associated with hyperhomocysteinemia, but not with coronary artery disease.