Candidate genes for nonsyndromic cleft lip and palate and maternal cigarette smoking and alcohol consumption: Evaluation of genotype-environment interactions from a population-based case-control study of orofacial clefts

Previous studies suggest that the relationship between genes and nonsyndrom ic cleft lip +/- cleft palate (CLP) or cleft palate only (CP) may be modifi ed by the environment. Using data from a population-based case-control stud y, we examined allelic variants for three genes, i.e., transforming growth factor alpha (TGFA), transforming growth factor beta 3 (TGFB3), and Msh (Dr osophila) homeobox homolog 1 (MSX1), and their interactions with two exposu res during pregnancy (maternal cigarette smoking and alcohol consumption) a s risk factors for CLP and CP. For each cleft phenotype, risk estimates ass ociated with most allelic variants tended to be near unity. Risk estimates for maternal smoking (greater than or equal to 10 cigarettes/day) were sign ificantly elevated for CP and were most elevated among infants with allelic variants at the TGFB3 or MSX1 sites. By comparison, risk estimates for mat ernal alcohol consumption (greater than or equal to 4 drinks/month) were si gnificantly elevated for CLP and were most elevated among infants with alle lic variants at the MSX1 site. Our results suggest that development of CLP and CP may be influenced independently by maternal exposures but more signi ficantly by interaction of such exposures and specific allelic variants. Te ratology 59. 39-50, 1999. (C) 1999 Wiley-Liss, Inc.