TESTING FOR INTERACTION BETWEEN MATERNAL SMOKING AND TGFA GENOTYPE AMONG ORAL CLEFT CASES BORN IN MARYLAND 1992-1996

Objective: Infants born in Maryland between June 1992 and June 1996 we re used in a case-control study of nonsyndromic oral clefts to test fo r effects of maternal smoking and a polymorphic genetic marker at the transforming growth factor alpha (TGFA) locus, both of which have been reported to be risk factors for these common birth defects. Design an d Setting: Cases were infants with an oral cleft ascertained through t hree comprehensive treatment centers, with additional ascertainment th rough a registry of birth defects maintained by the Maryland Hearth De partment. Controls were healthy infants. Medical history information o n infants and mothers were collected, along with DNA samples. Patients , Participants: Among 286 cases contacted (72% ascertainment), there w ere 192 nonsyndromic isolated oral clefts (Ins M; 86 F) available for this case-control study. Main Outcome Measures: The largest group of 1 49 Caucasian nonsyndromic cases and 86 controls was used to test for a ssociation with maternal smoking and genotype at the Taq1 polymorphism in TGFA. Results: While this modest sample had limited statistical po wer to detect gene-environment interaction, there was a significant ma rginal increase in risk of having an oral cleft if the mother smoked ( odds ratio = 1.75, 95%Cl = 1.01 to 3.02). We could not demonstrate sta tistical interaction between maternal smoking and TGFA genotype in thi s study, however, and the observed increase in the C2 allele among cas es was not statistically significant. Conclusions:We could not confirm either the reported association between oral clefts and TGFA genotype or its interaction with maternal smoking. However, these data do show an increased risk if the mother smoked during pregnancy, and this eff ect was greatest among infants with a bilateral cleft and no close fam ily history of clefts.