State Key Laboratory of Oral Diseases, Department of Cleft Lip and Palate, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, CA, USA.
J Oral Pathol Med. 2018 Jul;47(6):620-626. doi: 10.1111/jop.12719. Epub 2018 May 30.
Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a complex disorder, and it results from both of the genetic modifiers and environmental factors, with genetic modifiers contributes to it more than environmental factors. GWASs made great progress in identifying the candidate genes for NSCL/P, but the findings need to be replicated in other populations. In this study, we selected eleven SNPs from recent GWASs and GWAS meta-analysis to investigate their associations among 308 NSCL/P trios (134 non-syndromic cleft lip only (NSCLO) trios and 174 non-syndromic cleft lip with cleft palate (NSCLP) trios) from Han Chinese population. All SNPs were genotyped using SNPscan method and analyzed the data with FBAT, PLINK, and R package. Allelic TDT analysis showed that allele A at rs12543318 was associated with NSCLO trios (P = .0032, OR = 0.57, 95% CI: 0.39-0.83), and parent-of-origin effect analysis indicated that allele A at rs12543318 was significantly maternally undertransmitted among NSCLO (P = .0046), which implied the potential influence of genomic imprinting; global TDT further confirmed this association. Individual genotypic TDT showed homozygote C/C at rs12543318 was overtransmitted among NSCLO (Z = 3.79, P = .00015) and NSCL/P groups (Z = 3.83, P = .00013), which indicated that it could increase the risk to have cleft babies. Our findings indicated that rs12543318 was associated with NSCLO from Western Han Chinese population, which will give new scientific evidence for later researches in the etiology of NSOCs.
非综合征性唇裂伴或不伴腭裂（NSCL/P）是一种复杂的疾病，它既受遗传修饰因子的影响，也受环境因素的影响，遗传修饰因子的影响大于环境因素。GWAS 在确定 NSCL/P 的候选基因方面取得了重大进展，但这些发现需要在其他人群中进行复制。在这项研究中，我们从最近的 GWAS 和 GWAS 荟萃分析中选择了 11 个 SNP，以研究它们在来自汉族的 308 个 NSCL/P 三体型（134 个非综合征性单纯唇裂（NSCLO）三体型和 174 个非综合征性唇裂伴腭裂（NSCLP）三体型）中的关联。所有 SNP 均采用 SNPscan 方法进行基因分型，并使用 FBAT、PLINK 和 R 包分析数据。等位基因 TDT 分析显示，rs12543318 处的等位基因 A 与 NSCLO 三体型相关（P =.0032，OR = 0.57，95%CI：0.39-0.83），并且亲源效应分析表明，rs12543318 处的等位基因 A 在 NSCLO 中显著呈母系低传递（P =.0046），这暗示了基因组印记的潜在影响；全局 TDT 进一步证实了这种关联。个体基因型 TDT 显示，rs12543318 处的纯合子 C/C 在 NSCLO 中过度传递（Z = 3.79，P =.00015）和 NSCL/P 组中过度传递（Z = 3.83，P =.00013），这表明它可能增加生出唇裂婴儿的风险。我们的研究结果表明，rs12543318 与来自中国西部汉族的 NSCLO 相关，这将为非综合征性唇腭裂的病因学研究提供新的科学依据。
