Protective effect against alcohol dependence of the thermolabile variant of MTHFR.
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.


CONCLUSIONS
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.
Saffroy
Raphaël
R
Service de Biochimie et Biologie moléculaire, INSERM 602, Université Paris XI, Hôpital Paul Brousse, Assistance Publique-Hôpitaux de Paris, 94800 Villejuif, France. raphael.saffroy@pbr.ap-hop-paris.fr <raphael.saffroy@pbr.ap-hop-paris.fr>
Benyamina
Amine
A
Pham
Patrick
P
Marill
Cathy
C
Karila
Laurent
L
Reffas
Maâmar
M
Debuire
Brigitte
B
Reynaud
Michel
M
Lemoine
Antoinette
A
D000428:Alcohol Drinking / Q000235:genetics; D020269:Alcoholic Neuropathy / Q000235:genetics; D000437:Alcoholism / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D035061:Control Groups; D005260:Female; D005492:Folic Acid / Q000097:blood; D005494:Folic Acid Deficiency / Q000097:blood / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000235:genetics; D008108:Liver Diseases, Alcoholic / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012306:Risk; D014805:Vitamin B 12 / Q000097:blood
D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12