Mutation at Paired box gene 9 is associated with non-syndromic cleft lip only from Western Han Chinese population

This study aimed to initially screen more susceptible variations at PAX9 gene in non-syndromic cleft palate only cases and then test their associations in independent non-syndromic orofacial cleft subtypes from Western Han Chinese population.

Initially exons at PAX9 gene were screened for variations among 180 non-syndromic cleft palate only patients by the Sanger sequencing method, and the genotype data from 1000 Genomes Project Database was taken as control to perform Chi-square test. Subsequently, we performed association analysis among 2202 non-syndromic orofacial cleft patients (938 non-syndromic cleft palate only cases, 456 non-syndromic cleft lip only cases and 808 non-syndromic cleft lip and palate cases) and 1823 normal controls to replicate the role of two significant single nucleotide polymorphisms.

Two intronic single nucleotide polymorphism rs12885612 (P = 0.047, OR = 0.671 and 95-0.996) and rs12881248 (P = 0.047, OR = 1.006 and 95 %CI: 0.443-0.995) were associated non-syndromic cleft palate only in the initial screen phase. Surprisingly, in replication analysis rs12885612 (P = 0.048, OR = 1.25, 95 %CI: 1.0-1.56) and rs12881248 (P = 0.037, OR = 1.26, 95 %CI: 1.01-1.57) exhibited significant association signal in non-syndromic cleft lip only group, but not in non-syndromic cleft palate only group.

In summary, this study firstly revealed that rs12885612 and rs12881248 at PAX9 gene associated with non-syndromic cleft lip only from Western Han Chinese population, which indicated that PAX9 is a promising susceptible gene for non-syndromic cleft lip only in Western Han Chinese population.