INFANT TGF-ALPHA GENOTYPE, OROFACIAL CLEFTS, AND MATERNAL PERICONCEPTIONAL MULTIVITAMIN USE

Objective: We previously demonstrated a strong association between per iconceptional maternal cigarette smoking, infant transforming growth f actor-alpha (TGFa) genotype, and risk of orofacial clefts. Because ser um folate may be decreased by cigarette smoking and because maternal p ericonceptional use of multivitamins containing folic acid has been as sociated with a reduced risk of clefting, we explored whether a potent ial relation existed between infant TGFa genotype, maternal multivitam in use, and risk of orofacial cleft phenotypes. Design: Data were deri ved from a population-based case-control study of fetuses and live-bor n infants among a cohort of 1987 to 1989 California births (n = 548,84 4). Information concerning periconceptional multivitamin use was obtai ned via telephone interviews with mothers of 731 (84.7% of eligible) o rofacial cleft case infants, and of 734 (78.2%) nonmalformed control i nfants. DNA was obtained from newborn screening bloodspots and genotyp ed for the Taq1 polymorphism of TGFa. Among infants of interviewed mot hers, genotypes were available for 571 (78.1%) case infants and 640 (8 7.2%) control infants. Setting: The study encompassed all hospitals in selected California counties. Main Outcome Measure: The main outcome measures were the risks of specific cleft phenotypes among infants wit h uncommon TGFa genotypes and whose mothers did not use multivitamins periconceptionally. Results: Compared with infants homozygous for the common TGFa genotype and whose mothers used multivitamins, increased c lefting risks were observed for infants with the A2 genotype (homozygo us or heterozygous) and whose mothers did not use multivitamins. Risk estimates were 3.0 (1.4-6.6 [95% confidence interval]) for isolated cl eft lip with or without cleft palate (CLP), 2.4 (0.69-11.6) for multip le CLP, 2.6 (0.97-7.7) for isolated cleft palate (CP), 4.2 (1.3-16.2) for multiple CP, and 8.1 (2.6-27.7) for ''known-syndrome'' clefts. Cle fting risks for infants with the A2 genotype and whose mothers used mu ltivitamins were substantially smaller, as were the risks for infants with the A1 genotype whose mothers did not use multivitamins. Conclusi on: These data provide preliminary evidence for a gene-nutrient intera ction in risk of clefting.