title: Genetic susceptibilities in the association between maternal exposure to tobacco smoke and the risk of nonsyndromic oral cleft.
abstract: Maternal tobacco consumption is considered as a risk factor for nonsyndromic oral clefts. However, this risk is moderate and may be modulated by genetic susceptibilities, including variants of the TGFA, TGFB3 and MSX1 developmental genes and polymorphisms of genes of the CYP (1A1, 2E1) and GST (M1, T1) families involved in metabolic pathways of tobacco smoke compounds. This French case-control study (1998-2001; 240 nonsyndromic cases, 236 controls) included a case-parent design (175 triad-families) that made it possible to distinguish the direct effect of the child's genotype and maternally mediated effects. Maternal smoking during the first trimester of pregnancy was not associated with the oral cleft risk in this population, but we observed statistically significant increased risks associated with maternal exposure to environmental tobacco smoke (ETS). No variant of any of the three developmental genes was significantly associated with oral cleft. The fetal CYP1A1*2C variant allele was associated with a statistically significant decreased risk, compared with the homozygous wild-type: relative risk = 0.48, 95% confidence interval: 0.2, 1.0. Suggestive reduced risks were also observed for the maternal CYP1A1*2C allele and the fetal CYP2E1*5 allele. The GSTM1 and GSTT1 deletions appeared to play no role. Our findings suggest some interactions, with the strongest between ETS and CYP1A1 or MSX1 and between maternal smoking and CYP2E1. We did not confirm the maternal smoking-infant GSTT1 null interaction previously reported by other investigators.
authors.affiliation: INSERM U625, Université de Rennes I, GERHM, Rennes, France. cecile.chevrier@rennes.inserm.fr
authors.forename: Cécile
authors.initials: C
authors.lastname: Chevrier
authors.forename: Michel
authors.initials: M
authors.lastname: Bahuau
authors.forename: Claire
authors.initials: C
authors.lastname: Perret
authors.forename: David M
authors.initials: DM
authors.lastname: Iovannisci
authors.forename: Agnès
authors.initials: A
authors.lastname: Nelva
authors.forename: Christine
authors.initials: C
authors.lastname: Herman
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Vazquez
authors.forename: Christine
authors.initials: C
authors.lastname: Francannet
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Robert-Gnansia
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Lammer
authors.forename: Sylvaine
authors.initials: S
authors.lastname: Cordier
mesh_terms: D016022:Case-Control Studies; D002971:Cleft Lip / Q000453:epidemiology / Q000235:genetics*; D002972:Cleft Palate / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D018811:Maternal Exposure; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012307:Risk Factors; D012906:Smoke; D012907:Smoking / Q000009:adverse effects; D014026:Nicotiana
chemical_list: D012906:Smoke; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase