Variants of developmental genes (TGFA, TGFB3, and MSX1) and their associations with orofacial clefts: A case‐parent triad analysis

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Abstract
We selected 262 case‐parent triads from a population‐based study of orofacial clefts in Norway, and examined variants of developmental genes TGFA, TGFB3, and MSX1 in the etiology of orofacial clefts. One hundred seventy‐four triads of cleft lip cases (CL±P) and 88 triads of cleft palate only cases (CPO) were analyzed. There was little evidence for an association of any of these genes with CL±P. The strongest association was a 1.7‐fold risk with two copies of the TGFB3‐CA variant (95% CI=0.9–3.0). Among CPO cases, there was a 3‐fold risk with two copies of the TGFA TaqI A2 allele, and no increase with one copy. Assuming this to be a recessive effect, we estimated a 3.2‐fold risk among babies homozygous for the variant (95% CI=1.1–9.2). Furthermore, there was strong evidence of gene‐gene interaction. While there was only a weak association of the MSX1‐CA variant with CPO, the risk was 9.7‐fold (95% CI=2.9–32) among children homozygous for both the MSX1‐CA A4 allele and the TGFA A2 allele. No association of CPO with the TGFA variant was seen among the other MSX1‐CA genotypes. In conclusion, no strong associations were found between CL±P and variants at these three genes. There was a possible recessive effect of the TGFA TaqI variant on the risk of CPO, with a 3‐fold risk among children homozygous for the variant. The effect of this TGFA genotype was even stronger among children homozygous for the MSX1‐CA A4 allele, raising the possibility of interaction between these two genes. Genet Epidemiol 24:230–239, 2003.
Funding Information
  • Medical Birth Registry of Norway
  • Locus for Registry Epidemiology, University of Bergen
  • U.S. National Institute of Environmental Health Sciences
  • U.S. National Institutes of Health (DE08559, DE11948)
  • Norwegian Research Council

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