Thermolabile Methylenetetrahydrofolate Reductase (MTHFR) Gene as a Risk Factor for Cardiovascular Disease in the Female

Abstract

Background: A thermolabile mutant of methylenetetrahydrofolate reductase has been associated with elevated levels of total plasma homocysteine. The fact that hyperhomocysteinemia is a risk factor for coronary heart disease, stroke, and venous thrombosis, has led to communications that carriers of the thermolabile MTHFR gene have increased risk of premature cardiovascular disease. However, contradictory observations have also been reported. Methods and results: We assessed the risk of this mutation for cardiovascular disease (CAD) by studying 175 patients, of which 89 patients has acute myocardial infarction, old myocardial injury, bypass surgery, or angioplasty. The other 86 patients served as controls with similar demographics. Analysis of the thermolabile MTHFR C667T mutant showed a genotype distribution of 49.4%, 40.4%, and 10.0%, respectively, for homozygous normal (-/-), heterozygous (+/-), and homozygous mutant (+/+) cases, comparable to the control group: 56.9%, 40.7%, and 2.3% (P=0.105). In terms of gender distribution, the male cases had a thermolabile allele frequency of 21.3% compared to the male control of 23.3% (P=0.736), the female case had an allele frequency of 40.5% compared to the female control of 22.0% (P=0.010). Conclusions: In this study, we have found that there is a significant risk association between the mutant carrier and CAD for the female gender, whereas there is no such association for the male population. This gender preference may explain the discordant reports of thermolabile MTHFR as a risk factor for CAD.