Gene-gene interaction between MSX1 and TP63 in Asian case-parent trios with nonsyndromic cleft lip with or without cleft palate.
Gene-gene interaction between MSX1 and TP63 in Asian case-parent trios with nonsyndromic cleft lip with or without cleft palate.
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DOI：
10.1002/bdr2.1139
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发表时间：
2018-03
影响因子：
2.1
通讯作者：
Dongjing Liu;H. Schwender;Mengying Wang;Hong Wang;Ping Wang;Hongping Zhu;Zhibo Zhou;Jing Li;Tao Wu;T. Beaty
中科院分区：
文献类型：
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作者：
Dongjing Liu;H. Schwender;Mengying Wang;Hong Wang;Ping Wang;Hongping Zhu;Zhibo Zhou;Jing Li;Tao Wu;T. Beaty
背景小泛素样修饰，也称为苏素化，是参与唇和腭发育的重要翻译后调节机制。最近的研究报道了两个 SUMO 化靶基因 MSX1 和 TP63，在与非综合征性唇裂相关的测试中已达到全基因组水平的显着性。在这里，我们对 SUMO1、MSX1 和 TP63 进行了考虑基因-基因和基因-环境相互作用的候选基因分析，以进一步探讨伴有或不伴有腭裂的非综合征性唇裂 (NSCL/P) 的病因学。方法 通过国际联盟确定的 1,038 个亚洲 NSCL/P 三人组中，对 SUMO1、MSX1 和 TP63 内或附近的总共 130 个单核苷酸多态性 (SNP) 进行了分析。使用条件逻辑回归模型来探索涉及母亲环境烟草烟雾和多种维生素补充剂的基因-基因（G × G）和基因-环境（G × E）相互作用。 Bonferroni 校正用于 G × E 分析，排列检验用于 G × G 分析。结果虽然传递不平衡测试和基因-环境相互作用分析没有显示显着的结果，但我们确实发现了MSX1和TP63附近的SNP之间的基因-基因相互作用的信号。三个成对相互作用在排列测试中产生显着的p值（rs884690和rs9290890，p = 9.34 × 10-5和经验p = 1.00 × 10-4，rs1022136和rs4687098，p = 2.41 × 10-4和经验p = 2.95 × 10-4， rs6819546 和 rs9681004，p = 5.15 × 10-4 和经验 p = 3.02 × 10-4 ）。结论 MSX1 和 TP63 之间的基因-基因相互作用可能影响亚洲人群患 NSCL/P 的风险。我们的研究提供了对 NSCL/P 遗传病因学的进一步了解，并强调了在这种常见颅面畸形的病因学中考虑基因-基因相互作用的重要性。
BACKGROUND Small ubiquitin-like modification, also known as sumoylation, is a crucial post-translational regulatory mechanisms involved in development of the lip and palate. Recent studies reported two sumoylation target genes, MSX1 and TP63, to have achieved genome-wide level significance in tests of association with nonsyndromic clefts. Here, we performed a candidate gene analysis considering gene-gene and gene-environment interaction for SUMO1, MSX1, and TP63 to further explore the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P). METHODS A total of 130 single-nucleotide polymorphisms (SNPs) in or near SUMO1, MSX1, and TP63 was analyzed among 1,038 Asian NSCL/P trios ascertained through an international consortium. Conditional logistic regression models were used to explore gene-gene (G × G) and gene-environment (G × E) interaction involving maternal environmental tobacco smoke and multivitamin supplementation. Bonferroni correction was used for G × E analysis and permutation tests were used for G × G analysis. RESULTS While transmission disequilibrium tests and gene-environment interaction analysis showed no significant results, we did find signals of gene-gene interaction between SNPs near MSX1 and TP63. Three pairwise interactions yielded significant p values in permutation tests (rs884690 and rs9290890 with p = 9.34 × 10-5 and empirical p = 1.00 × 10-4 , rs1022136 and rs4687098 with p = 2.41 × 10-4 and empirical p = 2.95 × 10-4 , rs6819546 and rs9681004 with p = 5.15 × 10-4 and empirical p = 3.02 × 10-4 ). CONCLUSION Gene-gene interaction between MSX1 and TP63 may influence the risk of NSCL/P in Asian populations. Our study provided additional understanding of the genetic etiology of NSCL/P and underlined the importance of considering gene-gene interaction in the etiology of this common craniofacial malformation.