20号染色体长臂12区的基因变异导致了非综合征性口面部裂隙易感性。

Genetic variants of 20q12 contributed to non-syndromic orofacial clefts susceptibility.

作者信息

Yin X, Ma L, Li Y, Xu M, Wang W, Wang H, Yuan H, Du Y, Li S, Ma J, Jiang H, Wang L, Zhang W, Pan Y

机构信息

Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.

出版信息

Oral Dis. 2017 Jan;23(1):50-54. doi: 10.1111/odi.12570. Epub 2016 Sep 13.

DOI:10.1111/odi.12570

PMID:27537108

Abstract

OBJECTIVE

Previous genomewide association studies (GWAS) identified a region near MAFB at chr20q12 associated with non-syndromic orofacial clefts (NSOC) susceptibility. However, whether other SNPs in this area could independently contribute to non-syndromic orofacial clefts in Chinese populations remained obscure.

MATERIALS AND METHODS

We selected 24 SNPs based on a haplotype-tagging SNP strategy and evaluated their associations with risk of non-syndromic orofacial clefts in a large-scale two-stage case-control study with 1278 cases and 1295 controls. Genotyping was performed with Sequenom and TaqMan assay. Associations between the SNPs and risk of non-syndromic orofacial clefts were estimated from unconditional logistic regression analyses.

RESULTS

Overall, six SNPs were found to be the susceptible factors of non-syndromic orofacial clefts. The most significant and independent SNP was rs6129653 (additive model of P value = 1.4E-06). In subgroup analysis, its significant associations with cleft lip only (CLO) and cleft lip and palate (CLP) were observed. Furthermore, in silico bioinformatics analysis indicated that rs6129653 was located in the transcriptionally active region and associated with MAFB expression in human brain tissues.

CONCLUSIONS

Rs6129653 was an independent locus of non-syndromic orofacial clefts among Chinese populations possibly due to its potential of distal transcriptional regulation of MAFB expression.

摘要

目的

先前的全基因组关联研究（GWAS）确定了位于20号染色体q12区MAFB附近的一个区域与非综合征性口面部裂隙（NSOC）易感性相关。然而，该区域的其他单核苷酸多态性（SNP）是否能独立影响中国人群的非综合征性口面部裂隙尚不清楚。

材料与方法

我们基于单倍型标签SNP策略选择了24个SNP，并在一项大规模两阶段病例对照研究中评估了它们与非综合征性口面部裂隙风险的关联，该研究包括1278例病例和1295例对照。采用Sequenom和TaqMan检测法进行基因分型。通过无条件逻辑回归分析估计SNP与非综合征性口面部裂隙风险之间的关联。

结果

总体而言，发现6个SNP是非综合征性口面部裂隙的易感因素。最显著且独立的SNP是rs6129653（加性模型，P值 = 1.4E - 06）。在亚组分析中，观察到其与单纯唇裂（CLO）和唇腭裂（CLP）有显著关联。此外，电子生物信息学分析表明，rs6129653位于转录活性区域，与人脑组织中MAFB的表达相关。