Thyroid cancer causal gene FOXE 1 involved in orofacial clefts in Western Han Chinese

FOXE1 is causal gene for thyroid cancer and has been identified to play an essential role in non-syndromic orofacial clefts (NSOCs) among European population, but its effects remain controversial in Chinese Han population. To investigate its roles among Western Han Chinese population, we selected three SNPs (single nucleotide polymorphism): rs894673, rs3758249 and rs4460498 at FOXE1 gene based on the published literatures and genotyped them in 440 case-parent trios by using SNPscan technology. We performed transmission disequilibrium test (TDT), pair-wise LD, sliding-window haplotype analysis and parent-of-origin effect analysis to evaluate the association. Allelic TDT results showed strong significance among NSOCs and NSCLP (Lowest P=0.0050) for all the three SNPs. Genotypic TDT results showed that A/A homozygotes at rs894673 and T/T homozygotes at rs3758249 were significantly under-transmitted from parents to affected individuals among NSOCs (lowest P=0.016), which indicated that they were protective for NSOCs. Rs894673 A allele (P=0.028), rs3758249 T allele (P=0.028), rs4460498 T allele (P=0.016) was paternally over-transmitted for NSOCs. LD results showed that they tightly linked with each other (D,>0.8 and r2>0.8), and several haplotypes display association with NSOCs and NSCLP. These SNPs at FOXE1 were associated with NSOCs among Western Han Chinese population, which could give more evidence of FOXE1 gene in NSOCs and new insights for future research.