State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cleft Lip and Palate, West China Hospital of Stomatology, Sichuan University, China.
Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, USA.
Arch Oral Biol. 2020 Sep;117:104829. doi: 10.1016/j.archoralbio.2020.104829. Epub 2020 Jul 10.
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.
本研究旨在初步筛选非综合征性腭裂患者 PAX9 基因中更易感的变异体，然后在西方汉族人群中非综合征性口面裂的独立亚型中检测其相关性。
首先通过 Sanger 测序法筛选 180 例非综合征性腭裂患者 PAX9 基因外显子中的变异体，并以 1000 基因组计划数据库中的基因型数据进行卡方检验。随后，我们对 2202 例非综合征性口面裂患者（938 例非综合征性腭裂、456 例非综合征性唇裂和 808 例非综合征性唇腭裂）和 1823 例正常对照进行关联分析，以复制两个显著单核苷酸多态性的作用。
两个内含子单核苷酸多态性 rs12885612（P=0.047，OR=0.671 和 95-0.996）和 rs12881248（P=0.047，OR=1.006 和 95%CI：0.443-0.995）在初始筛选阶段与非综合征性腭裂相关。令人惊讶的是，在复制分析中，rs12885612（P=0.048，OR=1.25，95%CI：1.0-1.56）和 rs12881248（P=0.037，OR=1.26，95%CI：1.01-1.57）在非综合征性唇裂组中表现出显著的关联信号，但在非综合征性腭裂组中没有。
总之，本研究首次揭示了 PAX9 基因中的 rs12885612 和 rs12881248 与西方汉族人群中非综合征性唇裂相关，表明 PAX9 是西方汉族人群中非综合征性唇裂的一个有前途的易感基因。
