ASSOCIATION STUDY OF TRANSFORMING GROWTH-FACTOR-ALPHA (TGF-ALPHA) TAQI POLYMORPHISM AND ORAL CLEFTS - INDICATION OF GENE-ENVIRONMENT INTERACTION IN A POPULATION-BASED SAMPLE OF INFANTS WITH BIRTH-DEFECTS

In this study of infants with isolated birth defects, 69 cleft palate only cases, 114 cleft lip with or without cleft palate cases, and 284 controls with noncleft birth defects (all born in Maryland between 198 4 and 1992) were examined to test for associations among maternal expo sures, genetic markers, and oral clefts. A significantly higher freque ncy of positive family history of birth defects among both groups of o ral cleft cases compared with controls was seen in these data. While t here was a modest increase in the less common C2 allele at the TaqI si te in the transforming growth factor alpha (TGF alpha) locus among cle ft palate only infants compared with the birth defect controls, the as sociation appeared to reflect an underlying interaction between matern al smoking and infant genotype. This apparent gene-environment interac tion was also found among those reporting no family history of any bir th defect. Infants carrying the rarer C2 allele who were exposed to ma ternal smoking of 10 or fewer cigarettes per day showed a 6.16-fold in crease in risk for cleft palate only (95% confidence interval 1.09-34. 7), while similar infants whose mothers smoked more than 10 cigarettes per day showed an 8.69-fold higher risk (95% confidence interval 1.57 -47.8). However, the dose-response relation was not significant.