Transmission analysis of TGFB1 gene polymorphisms in non-syndromic cleft lip with or without cleft palate

Transforming growth factor beta1 (TGF-β1) plays a significant role in craniofacial development. Previous linkage studies reported that the TGF-β1-locus at 19q13.1 harbour predisposing genes for non-syndromic oral clefts. In the present study case parents triads were evaluated to find the transmission effects of genetic variants in TGF- β1 towards non-syndromic cleft lip or palate (NSCL/P).

Using allelic discrimination method148 families (case-parent triads) were assessed for single nucleotide polymorphisms (SNPs) in TGF-β1 gene. The SNPs were checked for mendelian errors and Hardy-Weinberg equilibrium (HWE). Transmission disequilibrium test and haplotype frequencies were estimated.

The TGF-β1 SNPs showed very low minor allele frequencies (MAFs) and observed heterozygosity (Hobs). The transmission disequilibrium test (TDT) and parent-of-origin likelihood ratio tests (PO-LRT) were not significant for any of the SNPs tested. Strong linkage disequilibrium (r² = 0.722) was found between rs1800469 and rs1800470 SNPs. Haplotype analysis ignoring parent of origin showed strong evidence of excess transmission but it is not significant (p-value = 0.293).

Transmission of minor alleles were not observed from either parent indicating that the TGF-β1 gene polymorphisms by themselves do not confer risk for non-syndromic oral clefts but, rather, modify the stability and the activation process of TGF-β1. As the number of families included in the study are less, results must be considered still preliminary and require replication using more families.