Interaction between the ADH1C polymorphism and maternal alcohol intake in the risk of nonsyndromic oral clefts: an evaluation of the contribution of child and maternal genotypes.
BACKGROUND
Maternal alcohol consumption has been associated with an increased risk of nonsyndromic oral clefts in some studies. Study of gene-environment interaction may provide insight into the reasons for their discrepancies observed. We focused on a polymorphism of the ADH1C gene (third gene of the class I alcohol dehydrogenase family), involved in the metabolism of ethanol and other alcohols.


METHODS
Data come from a French case-control study (1998-2001), which tested the association between maternal alcohol consumption during the first trimester of pregnancy and the risk of nonsyndromic oral clefts (240 cases, 236 controls). A case-parent study design looked at the association with an ADH1C polymorphism (Ile349Val site) and potential gene-environment interaction effects. A log-linear model was used to distinguish the direct effect of the child's genotype from the maternally mediated effects.


RESULTS
An increased risk of nonsyndromic oral clefts was observed for women who reported drinking alcohol during the first trimester, compared with women who did not. The mutated ADH1C allele carried by the child seemed to have a protective effect against the risk of oral clefts (RRone copy, 0.71; 95% confidence interval [CI], 0.50-1.02; RRtwo copies, 0.63; 95% CI, 0.3-1.3). The maternal genotype played a less important role than the child's, and its action remains unclear. No significant evidence of interaction effects between the ADH1C genotype and maternal alcohol consumption was observed.


CONCLUSIONS
Because the ADH1C gene is involved in the metabolic pathways of many alcohols, we propose several hypotheses about the causal pathway, including ethanol oxidation activity and, more probably, retinol oxidation.
Chevrier
Cécile
C
Institut National de la Santé et de la Recherche Médicale (INSERM) U625, Rennes, France. cecile.chevrier@rennes.inserm.fr
Perret
Claire
C
Bahuau
Michel
M
Nelva
Agnès
A
Herman
Christine
C
Francannet
Christine
C
Robert-Gnansia
Elisabeth
E
Cordier
Sylvaine
S
D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking; D016022:Case-Control Studies; D002971:Cleft Lip / Q000139:chemically induced / Q000235:genetics*; D002972:Cleft Palate / Q000139:chemically induced / Q000235:genetics*; D005260:Female; D005315:Fetal Diseases / Q000139:chemically induced / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012307:Risk Factors
C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase