SNPs at TP63 gene was specifically associated with right-side cleft lip in Han Chinese population

Objectives Non-syndromic cleft lip with or without palate is one of the most common birth malformations.TP63andGREM1were recently reported to be associated with NSCL/P. However, there were few studies focused on their associations in non-syndromic cleft lip only (NSCLO). Design Initial screening and replication in large cohorts were used to locate the susceptible SNPs ofTP63andGREM1. Firstly, variations were screened among 192 NSCLO cases by the Sanger sequencing. Then, we selected five associated SNPs in initial screening phase and replicated among 1,006 NSCLO cases and 1,823 normal controls. Results Initial chi-square test showed that rs7653848, rs7624324, rs6790167, and rs1345186 inTP63and rs2280738 inGREM1achieved statistical significance (p < .05); the subsequent replication analysis showed that rs1345186 was specifically significant in right-side cleft lip (RCL;p = .017, OR = 1.33, and 95% CI: 1.05-1.69). Conclusion This study firstly used the subphenotype of cleft lip samples to verify the association betweenTP63andGREM1, which indicated thatTP63is a promising susceptible gene for RCL in Chinese population. And further 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.

Automated summary

This study verified the association between TP63 and GREM1 by using the subphenotype of cleft lip samples, indicating TP63 as a promising susceptible gene for right-side cleft lip in the Chinese population. It further confirmed different etiology in right-sided cleft lip, left-sided cleft lip, and bilateral cleft lip of NSCLO, providing new references for future research and genetic counseling.