title: Variants of developmental genes (TGFA, TGFB3, and MSX1) and their associations with orofacial clefts: a case-parent triad analysis.
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.
authors.affiliation: Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway. Astanand.Jugessur@molmed.uib.no
authors.forename: Astanand
authors.initials: A
authors.lastname: Jugessur
authors.forename: Rolv T
authors.initials: RT
authors.lastname: Lie
authors.forename: Allen J
authors.initials: AJ
authors.lastname: Wilcox
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
authors.forename: Jack A
authors.initials: JA
authors.lastname: Taylor
authors.forename: Ola D
authors.initials: OD
authors.lastname: Saugstad
authors.forename: Hallvard A
authors.initials: HA
authors.lastname: Vindenes
authors.forename: Frank
authors.initials: F
authors.lastname: Abyholm
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D005801:Genes, Homeobox / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008423:Maternal Age; D009664:Norway / Q000453:epidemiology; D011159:Population Surveillance; D012307:Risk Factors; D016211:Transforming Growth Factor alpha / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta