We performed a meta-analysis of the association of transforming growth factor α gene (TGFA) polymorphisms with the risk of cleft lip with or without cleft palate (CL/P) or cleft palate (CP).
To investigate the association between the TGFA:c.3851T > C (rs11466285) and TGFA:c.3822G > A (rs3771523) single-nucleotide polymorphisms (SNPs) and nonsyndromic cleft lip and/or cleft palate (CL/P) with microarray in north China.
Associations were found between the TGFA gene marker rs2166975 and nonsyndromic cleft palate only (CPO) phenotype (p = 0.045, df 1) as well as between the D2S292 marker and the cleft lip with or without cleft palate (CL/CP) phenotype in allele-wise TDT (P = 0.005, df 9) and genotype-wise TDT (P = 0.021, df 24).
While maternal smoking was a consistent risk factor for both CL/P and CP across all studies, the suggestive evidence for gene-environment interaction between the infant's genotype at the Taq1 marker in TGFA and maternal smoking was limited to CP.
We have previously reported a threefold risk of cleft palate only (CPO) among children homozygous for the less common allele A2 at the TaqI marker site of the transforming growth factor alpha gene (TGFA) (Jugessur et al.[2003a] Genet.Epidemiol.24:230-239).
Using data from a population-based case-control study, we examined allelic variants for three genes, i.e., transforming growth factor alpha (TGFA), transforming growth factor beta 3 (TGFB3), and Msh (Drosophila) homeobox homolog 1 (MSX1), and their interactions with two exposures during pregnancy (maternal cigarette smoking and alcohol consumption) as risk factors for CLP and CP.
Parents of children with CL(P) and CP showed an increased frequency of the TGFalpha/TaqI C2 allele (RR=4.10, p=0.009) relative to the comparison group.
This conclusion is in agreement with previous studies which showed a significant association between alleles of transforming growth factor alpha and CP only in humans, and that single recessive genes may play a crucial role during palatogenesis in mice as well as in Brittany spaniels.
We illustrate the methods by applying them to recent study of cleft palate in relation to maternal cigarette smoking and to a variant of the transforming growth factor alpha gene in the child.
Previous association studies using Caucasian populations of nonsyndromic cleft lip and/or palate (CL/P) and cleft palate only (CPO) have strongly suggested a role for TGFA in the susceptibility of clefting in humans.
While there was a modest increase in the less common C2 allele at the TaqI site in the transforming growth factor alpha (TGF alpha) locus among cleft palate only infants compared with the birth defect controls, the association appeared to reflect an underlying interaction between maternal smoking and infant genotype.
We carried out a retrospective association study to determine whether specific allelic variants of the TGFA gene are also associated with cleft palate only (CPO).