Jia Zhong-Lin, He Sha, Jiang Shu-Yuan, Zhang Bi-He, Duan Shi-Jun, Shi Jia-Yu, Huang Ning, Zhu Wen-Chao, Shi Bing
State Key Laboratory of Oral Disease, West China hospital of Stomatology, Sichuan University, Chengdu, PR China.
State Key Laboratory of Oral Disease, West China hospital of Stomatology, Sichuan University, Chengdu, PR China; Department of Cleft Lip and Palate Surgery, West China College of Stomatology, Sichuan University, Chengdu, PR China; Department of Stomatology, The third People's hospital of Chengdu, Chengdu, PR China.
Arch Oral Biol. 2017 Apr;76:14-19. doi: 10.1016/j.archoralbio.2016.12.010. Epub 2016 Dec 30.
Non-syndromic orofacial cleftings (NSOCs) are considered as complex trait, which results from genetic and/or environmental modifiers. Current findings could only explain small portion of the NSOCs. SOX9 gene plays an important role during craniofacial development in animal models and the Pierre Robin sequence (PRS). However, its role in non-syndromic clefts remains unknown.
In this study, we selected eight SNPs in and around SOX9 gene to make maximum coverage, and genotyped them by using RFLP-PCR and ligase detection reaction (LDR) methods to test its associations among 151 NSOCs (53 NSCLP, 52 NSCLO and 46 NSCPO) from Western Han Chinese population.
Allelic TDT results showed that G allele at rs12941170 of SOX9 was under-transmitted among NSOCs (p=0.00014, OR=0.55 and 95%CI: 0.40-0.75), which could indicate that the G allele is protective against NSOCs; parent-of-origin effect analysis showed that G allele at rs12941170 was maternally under-transmitted (p=0.002), while there was no statistically difference between the maternal and paternal transmission of it. To test if the adjacent SNPs travel together from parents to the affected individual, we carried out the sliding window haplotype analysis, it is interesting to find that the haplotypes carrying the G allele at rs12941170 also was under-transmitted for NSOCs, NSCL/P, NSCLP and NSCPO (lowest p=0.00033).
This study suggested that G allele at rs12941170 was protective, which could decrease the risk for NSOCs from Western Han Chinese population, and it will provide new reference for future research and genetic counseling in NSOCs.
非综合征性口面部裂隙（NSOCs）被视为复杂性状，由遗传和/或环境修饰因素导致。目前的研究结果仅能解释一小部分NSOCs。SOX9基因在动物模型的颅面发育和Pierre Robin序列（PRS）中起重要作用。然而，其在非综合征性腭裂中的作用尚不清楚。
在本研究中，我们在SOX9基因及其周围选择了8个单核苷酸多态性（SNP）以实现最大覆盖，并通过限制性片段长度多态性聚合酶链反应（RFLP-PCR）和连接酶检测反应（LDR）方法对其进行基因分型，以检测其与151例来自西汉汉族人群的NSOCs（53例非综合征性唇腭裂（NSCLP）、52例非综合征性唇腭裂（NSCLO）和46例非综合征性腭裂（NSCPO））之间的关联。
等位基因传递不平衡检验（TDT）结果显示，SOX9基因rs12941170位点的G等位基因在NSOCs中传递不足（p = 0.00014，比值比（OR）= 0.55，95%置信区间（CI）：0.40 - 0.75），这可能表明G等位基因对NSOCs具有保护作用；亲源效应分析显示，rs12941170位点G等位基因的母系传递不足（p = 0.002），而其母系和父系传递之间无统计学差异。为了检测相邻的SNP是否从父母共同传递给受影响个体，我们进行了滑动窗口单倍型分析，有趣的是发现携带rs12941170位点G等位基因的单倍型在NSOCs、NSCL/P、NSCLP和NSCPO中也传递不足（最低p = 0.00033）。
本研究表明rs12941170位点的G等位基因具有保护作用，可降低西汉汉族人群患NSOCs的风险，为未来NSOCs的研究和遗传咨询提供新的参考。
