Gene-gene interaction between MSX1 and TP63 in Asian case-parent trios with nonsyndromic cleft lip with or without cleft palate

被引:8
作者
Liu, Dongjing [1 ]
Schwender, Holger [2 ]
Wang, Mengying [1 ]
Wang, Hong [1 ]
Wang, Ping [3 ]
Zhu, Hongping [4 ]
Zhou, Zhibo [4 ]
Li, Jing [4 ]
Wu, Tao [1 ,5 ]
Beaty, Terri H. [6 ]
机构
[1] Peking Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, 38 Xue Yuan Rd, Beijing, Peoples R China
[2] Heinrich Heine Univ Duesseldorf, Math Inst, Dusseldorf, Germany
[3] Beijing Ctr Dis Prevent & Control, Dept Stat & Informat, Beijing, Peoples R China
[4] Peking Univ, Sch Stomatol, Beijing, Peoples R China
[5] Minist Hlth, Key Lab Reprod Hlth, Beijing, Peoples R China
[6] Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA
基金
中国国家自然科学基金;
关键词
association study; case-parent trio; gene-gene interaction; nonsyndromic cleft lip with or without cleft palate; sumoylation; GENOME-WIDE ASSOCIATION; OROFACIAL CLEFTS; SUSCEPTIBILITY LOCUS; CODING VARIANTS; AND/OR PALATE; RISK; SUMO; SUMOYLATION; IDENTIFY; METAANALYSES;
D O I
10.1002/bdr2.1139
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
BackgroundSmall 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). MethodsA 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 x G) and gene-environment (G x E) interaction involving maternal environmental tobacco smoke and multivitamin supplementation. Bonferroni correction was used for G x E analysis and permutation tests were used for G x G analysis. ResultsWhile 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 x 10(-5) and empirical p=1.00 x 10(-4), rs1022136 and rs4687098 with p=2.41 x 10(-4) and empirical p=2.95 x 10(-4), rs6819546 and rs9681004 with p=5.15 x 10(-4) and empirical p=3.02 x 10(-4)). ConclusionGene-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.
引用
收藏
页码:317 / 324
页数:8
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