Protective effect against alcohol dependence of the thermolabile variant of MTHFR

Abstract

Background Hyperhomocysteinemia is frequently observed in alcohol-dependent subjects, in particularly in those with marked withdrawal symptoms. The common C677T transition on the methylenetetrahydrofolate reductase ( MTHFR) gene influences homocysteinemia. Our objective was to study the prevalence of the MTHFR C677T polymorphism in alcohol-dependent subjects and the influence of this polymorphism on symptoms associated with alcoholism. Methods MTHFR C677T polymorphism was determined in 93 control subjects and 242 alcohol-dependent subjects. Serum homocysteine, folate and vitamin B 12 levels together with hepatic biological parameters were determined in the control and alcohol-dependent subjects. Results Hyperhomocysteinemia is frequently observed in alcohol-dependent subjects, particularly in those with marked withdrawal symptoms. Alcohol-dependent subjects showed a significant decrease in MTHFR 677TT prevalence (9%, 21/242) compared to controls (18%, 17/93) ( p < 0.02). The relative risk estimated as an odds ratio for alcoholism in subjects with the TT genotype is 0.42 (odd ratio 95% confidence interval, 0.21–0.83). Moreover, drinkers with TT genotype presented lower values for markers of alcohol misuse ( p < 0.05), better liver function tests, a lower frequency of relapses and no marked withdrawal symptoms as assessed by the Lesch typology. Conclusion MTHFR 677TT genotype could play a protective role against alcohol dependence. Moreover, when subjects with MTHFR 677TT genotype become dependent to alcohol, they seem to constitute a subgroup of alcoholic patients with a decreased risk for developing neurotoxic withdrawal symptoms and hepatic toxicity.