Smoking, genetic polymorphisms in biotransformation enzymes, and nonsyndromic oral clefting: A gene-environment interaction

The importance of maternal smoking in the pathogenesis of oral facial cleft s is not clear. Susceptibility to cigarette smoke depends on biotransformat ion of the toxic compounds by mother and embryo. In a population-based case -control study, we investigated the effects of maternal smoking during the first pregnancy trimester and the interaction with polymorphisms in the bio transformation enzymes cytochrome P450 1A1 (CYP1A1) and glutathione S-trans ferase theta 1-1 (GSTT1) on the risk of nonsyndromic oral clefting in the o ffspring. We recruited 113 infants with nonsyndromic oral clefts and their mothers, as well as 104 control infants and their mothers. Maternal smoking habits were collected regarding the period 3 months before through 3 month s after conception. Buccal swabs were taken from mothers and infants for ge netic analysis. Maternal smoking was not strongly associated with oral clef ting (odds ratio = 1.1; 95% confidence interval = 0.6-2.2), nor were CYP1A1 and GSTT1 polymorphisms. Mothers who smoked and carried the GSTT1-null gen otype, however, had an increased risk for having a child with oral clefting compared with nonsmokers with the wild type genotype (odds ratio = 3.2; 95 % confidence interval 0.9-11.6). The risk was almost five times greater (od ds ratio 4.9; 95% confidence interval = 0.7-36.9) in mothers and infants bo th having the GSTT1-null genotype compared with both having the wild genoty pe. There was no interaction between CYP1A1 and maternal. smoking in relati on to oral clefting.