Am J Epidemiol 2003; 158:69-76.
Copyright © 2003 by Johns
Hopkins Bloomberg School of Public Health
ORIGINAL CONTRIBUTIONS |
Retinoic Acid Receptor Alpha Gene Variants, Multivitamin Use, and Liver Intake as Risk Factors for Oral Clefts: A Population-based Case-Control Study in Denmark, 1991–1994
1 Department of Biomedical Sciences, Baylor College of Dentistry, The Texas A&M University System Health Science Center, Houston, TX.
2 Institute of Biosciences and Technology, The Texas A&M University System Health Science Center, Houston, TX.
3 Department of Pediatrics, University of Iowa, Iowa City, IA.
4 Center for Prevention of Congenital Malformations, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
Previous studies suggest that the risks of nonsyndromic cleft lip with or without cleft palate (CL±P) and isolated cleft palate are influenced by variation at several loci and that these loci interact with environmental factors to determine disease risk. One putative genetic risk factor for these conditions is the retinoic acid receptor alpha (RARA) locus, which is involved in cell-specific responses to retinoic acid. Hence, RARA may influence disease risk via an interaction with vitamin A and related compounds. Data from a Danish case-control study (1991–1994) were used to evaluate the relations between oral clefts, RARA, and maternal vitamin A exposure from multivitamins and liver. Analyses provided no compelling evidence that the risks of CL±P or isolated cleft palate are related to the RARA variant analyzed. Consistent with several previous studies, the authors’ analyses indicated that maternal multivitamin supplement use protects against CL±P. Within the range observed in this population, higher levels of vitamin A intake from multivitamins and liver sources also seemed to protect against CL±P. Exploratory analyses suggested that the latter association was not entirely explained by the association between CL±P and multivitamin use, indicating that adequate levels of vitamin A may be required for normal development of the primary palate.
case-control studies; cleft lip; cleft palate; genetics; pregnancy; receptors, retinoic acid; vitamins
Abbreviations: Abbreviations: CI, confidence interval; CL±P, cleft lip with or without cleft palate; CP, isolated cleft palate; OR, odds ratio; RARA, retinoic acid receptor alpha; RE, retinol equivalents.
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