SNPs at TP63 gene was specifically associated with right-side cleft lip inHan Chinese population.

OBJECTIVES Non-syndromic cleft lip with or withoutpalateis one of the most common birth malformations. TP63 and GREM1 were recently reported to be associated with NSCL/P. However, there were few studies focusedon theirassociationsin non-syndromic cleft lip only (NSCLO). DESIGN Initial screening and replication in large cohorts were used to locate the susceptible SNPs of TP63 and GREM1.Firstly, variations were screened among 192 NSCLO cases by the Sanger sequencing. Then, we selected fiveassociated SNPs in initial screeningphase andreplicatedamong1006 NSCLO cases and 1823 normal controls. RESULTS Initial Chi-square test showed that rs7653848,rs7624324,rs6790167 and rs1345186inTP63 and rs2280738 in GREM1 achieved statistical significance (p<0.05);the subsequent replication analysis showed thatrs1345186was specificallysignificant in right side cleft lip (RCL) (P=0.017, OR=1.33 and 95%CI: 1.05-1.69). CONCLUSION This study firstly using the sub-phenotype of cleft lip samples to verify the association between TP63 and GREM1, which indicated that TP63 is a promising susceptible gene for RCL in Chinese population.Andfurther confirmed the different etiology in the right-sided cleft lip, left-sided cleft lip and bilateral cleft lip of NSCLO. This will give new reference for the future research and genetic counseling.