Protective effect against alcohol dependence of the thermolabile variant of MTHFR

• Published in: Drug and alcohol dependence 2008-07, Vol.96 (1), p.30-36
• Main Authors: Saffroy, Raphaël, Benyamina, Amine, Pham, Patrick, Marill, Cathy, Karila, Laurent, Reffas, Maâmar, Debuire, Brigitte, Reynaud, Michel, Lemoine, Antoinette
• Format: Article
• Language: English
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; Alcohol; Alcohol dependence; Alcohol Drinking - genetics; Alcoholic Neuropathy - genetics; Alcoholism; Alcoholism - blood; Alcoholism - enzymology; Alcoholism - genetics; Alcoholism and acute alcohol poisoning; Amino acids; Biological and medical sciences; Cell biology; Control Groups; Dependence; Drug addiction; Female; Folic Acid - blood; Folic Acid Deficiency - blood; Folic Acid Deficiency - genetics; Gene Frequency; Genetic factors; Genetic Predisposition to Disease - genetics; Genotype; Homocysteine; Homocysteine - blood; Humans; Hyperhomocysteinemia - blood; Hyperhomocysteinemia - genetics; Liver Diseases, Alcoholic - genetics; Male; Medical sciences; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Methylenetetrahydrofolate Reductase (NADPH2) - metabolism; Middle Aged; MTHFR; Polymorphism; Polymorphism, Genetic - genetics; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Risk; Toxicology; Vitamin B 12 - blood
• ISSN: 0376-8716; 1879-0046
• DOI: 10.1016/j.drugalcdep.2008.01.016

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 B12 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.