TPM1基因相关多态性与中国北方汉族人群非综合征性唇腭裂的相关研究

doi:10.3969/j.issn.1005-4979.2022.01.007

摘要/Abstract

摘要：

目的：分析TPM1基因上游功能区3个单核苷酸多态性（single nucleotide polymorphisms, SNPs）位点与中国北方人群非综合征性唇腭裂（nonsynodromic orofacial clefts, NSOC）的关联。方法：通过对335个NSOC样本及572个健康对照样本外周血DNA的研究对目的位点行聚合酶链反应（polymerase chain reaction, PCR）扩增、DNA测序、基因分型。利用PubMed数据库（https://www.ncbi.nlm.nih.gov/pubmed）采集相关多态性位点基本信息。使用SHEsis在线软件、SPSS 20.0软件对SNPs位点的等位基因频率、基因型及单体型进行分析研究。结果：TPM1相关rs1873147、rs7179658和rs4775599完全连锁，rs1873147在唇腭裂（cleft lip and palate, CLP）组与健康对照组之间的等位基因频率差异有统计学意义（P=0.035）。结论：TPM1相关rs7179658、rs1873147和rs477559与中国北方汉族人群NSOC可能存在关联。

关键词: 非综合征性唇腭裂, TPM1基因, 单核苷酸多态性

Abstract:

Objective: To analyze the association between three single nucleotide polymorphisms(SNPs) in the upstream functional region of TPM1 and nonsyndromic orofacial clefts(NSOC) in northern Chinese Han population. Methods: The peripheral blood DNA in 335 NSOC samples and 572 control samples were examined. The target sites were amplified by polymerase chain reaction(PCR), sequenced and genotyped. The basic information of polymorphic loci were collected from PubMed database (https://www.ncbi.nlm.nih.gov/pubmed). The allele frequency, genotype and haplotype of SNPs loci were analyzed by SHEsis and SPSS 20.0 software. Results: TPM1-related rs1873147, rs7179658 and rs4775599 were in complete linkage, and the allele frequency difference of rs1873147 between the cleft lip and palate(CLP) group and the healthy control group was statistically significant(P=0.035). Conclusion: TPM1-related rs7179658, rs1873147 and rs477559 may be associated with NSOC in the northern Chinese Han population.

Key words: nonsyndromic orofacial clefts, TPM1, single nucleotide polymorphism

回翔, 姜宇欣, 刘婷婷, 时旭恒, 王琪, 宋涛. TPM1基因相关多态性与中国北方汉族人群非综合征性唇腭裂的相关研究[J]. 《口腔颌面外科杂志》, 2022, 32(1): 34-41.

HUI Xiang, JIANG Yuxin, LIU Tingting, SHI Xuheng, WANG Qi, SONG Tao. Study on the association between TPM1 gene-related polymorphism and nonsyndromic orofacial clefts in the northern Chinese Han population[J]. 《Journal of Oral and Maxillofacial Surgery》, 2022, 32(1): 34-41.

https://journal06.magtech.org.cn/Jweb_joms/CN/Y2022/V32/I1/34

图/表 10

参考文献 22

[1]	Sarmiento K, Valencia S, Gracia G, et al. Clinical and epidemiologic description of orofacial clefts in Bogota and Cali, Colombia, 2001—2015[J]. Cleft Palate Craniofac J, 2018, 55(4): 517-520. doi: 10.1177/1055665617741062 URL
[2]	Liu XT, Yang SY, Meng LW, et al. Association between PTCH1 and RAD54B single-nucleotide polymorphisms and nonsyndromic orofacial clefts in a northern Chinese population[J]. J Gene Med, 2018, 20(12): e3055. doi: 10.1002/jgm.v20.12 URL
[3]	Razaghi-Moghadam Z, Namipashaki A, Farahmand S, et al. Systems genetics of nonsyndromic orofacial clefting provides insights into its complex aetiology[J]. Eur J Hum Genet, 2019, 27(2): 226-234. doi: 10.1038/s41431-018-0263-7 pmid: 30254216
[4]	Leśków A, Nawrocka M, Latkowska M, et al. Can contamination of the environment by dioxins cause craniofacial defects?[J]. Hum Exp Toxicol, 2019, 38(9): 1014-1023. doi: 10.1177/0960327119855121 pmid: 31169026
[5]	Zhang ZQ, Zhu ZM, Zhang BT, et al. Frequent mutation of rs13281615 and its association with PVT1 expression and cell proliferation in breast cancer[J]. Yi Chuan Xue Bao, 2014, 41(4): 187-195.
[6]	Birnbaum S, Ludwig KU, Reutter H, et al. Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24[J]. Nat Genet, 2009, 41(4): 473-477. doi: 10.1038/ng.333 pmid: 19270707
[7]	Yan J, Song H, Mi N, et al. Nucleotide variants of the NAT2 and EGF61 genes in patients in Northern China with nonsyndromic cleft lip with or without cleft palate[J]. Medicine (Baltimore), 2017, 96(37): e7973. doi: 10.1097/MD.0000000000007973 URL
[8]	Ludwig KU, Mangold E, Herms S, et al. Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci[J]. Nat Genet, 2012, 44(9): 968-971. doi: 10.1038/ng.2360 pmid: 22863734
[9]	Jia ZL, Leslie EJ, Cooper ME, et al. Replication of 13q31.1 association in nonsyndromic cleft lip with cleft palate in Europeans[J]. Am J Med Genet A, 2015, 167A(5): 1054-1060. doi: 10.1002/ajmg.a.36912 pmid: 25786657
[10]	Pan YC, Han Y, Zhang HC, et al. Association and cumulative effects of GWAS-identified genetic variants for nonsyndromic orofacial clefts in a Chinese population[J]. Environ Mol Mutagen, 2013, 54(4): 261-267. doi: 10.1002/em.21773 pmid: 23536526
[11]	Qian YJ, Li DD, Ma L, et al. TPM1 polymorphisms and nonsyndromic orofacial clefts susceptibility in a Chinese Han population[J]. Am J Med Genet A, 2016, 170A(5): 1208-1215. doi: 10.1002/ajmg.a.37561 pmid: 26792422
[12]	Geeves MA, Hitchcock-DeGregori SE, Gunning PW. A systematic nomenclature for mammalian tropomyosin isoforms[J]. J Muscle Res Cell Motil, 2015, 36(2): 147-153. doi: 10.1007/s10974-014-9389-6 URL
[13]	Matyushenko AM, Shchepkin DV, Susorov DS, et al. Structural and functional properties of αβ-heterodimers of tropomyosin with myopathic mutations Q147P and K49del in the β-chain[J]. Biochem Biophys Res Commun, 2019, 508(3): 934-939. doi: 10.1016/j.bbrc.2018.12.019 URL
[14]	Cirino AL, Ho C. Hypertrophic cardiomyopathy overview[J]. American Heart Journal, 1993, 95(4):511-520. doi: 10.1016/0002-8703(78)90244-2 URL
[15]	Liu J, Chen J, Yuan D, et al. Dynamic mRNA expression analysis of the secondary palatal morphogenesis in miniature pigs[J]. Int J Mol Sci, 2019, 20(17): E4284.
[16]	Xiong Y, Tang XF, Meng QS, et al. Differential expression analysis of the broiler tracheal proteins responsible for the immune response and muscle contraction induced by high concentration of ammonia using iTRAQ-coupled 2D LC-MS/MS[J]. Sci China Life Sci, 2016, 59(11): 1166-1176. pmid: 27761697
[17]	Zoupa M, Xavier GM, Bryan S, et al. Gene expression profiling in the developing secondary palate in the absence of Tbx1 function[J]. BMC Genomics, 2018, 19(1): 429. doi: 10.1186/s12864-018-4782-y pmid: 29866044
[18]	Chen Y, Hong ZX, Lu SS, et al. Downregulated expression of tropomyosin 1 in intrahepatic cholangiocarcinoma: A predictor of recurrence and prognosis[J]. Med Sci Monit, 2018, 24: 7875-7882. doi: 10.12659/MSM.907340 URL
[19]	Yao Q, Zhang W, Zhang TJ. Association of single nucleotide polymorphisms in the 3′UTR region of TPM1 gene with dilated cardiomyopathy: A case-control study[J]. Medicine (Baltimore), 2019, 98(44): e17710. doi: 10.1097/MD.0000000000017710 URL
[20]	Dunkhase E, Ludwig KU, Knapp M, et al. Nonsyndromic cleft lip with or without cleft palate and cancer: Evaluation of a possible common genetic background through the analysis of GWAS data[J]. Genom Data, 2016, 10: 22-29.
[21]	de Aquino SN, Messetti AC, Hoshi R, et al. Analysis of susceptibility polymorphisms for nonsyndromic cleft lip with or without cleft palate in the Brazilian population[J]. Birth Defects Res A Clin Mol Teratol, 2014, 100(1): 36-42. doi: 10.1002/bdra.v100.1 URL
[22]	高丽云, 李娜, 连贺强, 等. 表观遗传学在先天性唇腭裂发生中的作用机制研究进展[J]. 新乡医学院学报, 2020, 37(1): 8-11.

名称	位置
rs4775599	Chr15: 63 019 296
rs1873147	Chr15: 63 020 433
rs7179658	Chr15: 63 020 496
TPM1	Chr15: 63 042 698~63 071 915
间距	22 202~23 402

名称	位置
rs4775599	Chr15: 63 019 296
rs1873147	Chr15: 63 020 433
rs7179658	Chr15: 63 020 496
TPM1	Chr15: 63 042 698~63 071 915
间距	22 202~23 402

SNP	项目	人群	组别	样本量	参考等位基因	变异等位基因
rs7179658	1000 Genomes	全球	全组别范围	5 008	T=0.498	C=0.502
	1000 Genomes	东亚	亚组	1 008	T=0.863	C=0.137
	本研究	中国北方	亚组	572	T=0.844	C=0.156
rs1873147	1000 Genomes	全球	全组别范围	5 008	G=0.496	A=0.504
	1000 Genomes	东亚	亚组	1 008	G=0.860	A=0.140
	本研究	中国北方	亚组	572	G=0.844	A=0.156
rs4775599	1000 Genomes	全球	全组别范围	5 008	A=0.496	G=0.504
	1000 Genomes	东亚	亚组	1 008	A=0.860	G=0.140
	本研究	中国北方	亚组	572	A=0.844	G=0.166

SNP	项目	人群	组别	样本量	参考等位基因	变异等位基因
rs7179658	1000 Genomes	全球	全组别范围	5 008	T=0.498	C=0.502
	1000 Genomes	东亚	亚组	1 008	T=0.863	C=0.137
	本研究	中国北方	亚组	572	T=0.844	C=0.156
rs1873147	1000 Genomes	全球	全组别范围	5 008	G=0.496	A=0.504
	1000 Genomes	东亚	亚组	1 008	G=0.860	A=0.140
	本研究	中国北方	亚组	572	G=0.844	A=0.156
rs4775599	1000 Genomes	全球	全组别范围	5 008	A=0.496	G=0.504
	1000 Genomes	东亚	亚组	1 008	A=0.860	G=0.140
	本研究	中国北方	亚组	572	A=0.844	G=0.166

rs1873147	分组	基因型/[n（%）]			Chi²值	P值
rs1873147	分组	CC	CT	TT	Chi²值	P值
	对照组	411（71.9）	142（24.8）	18（3.1）	1.72	0.19
	NSOC组	249（74.3）	80（23.9）	6（1.8）	0.02	0.88
	CLO组	77（75.5）	22（21.6）	3（2.9）	0.81	0.37
	CLP组	75（80.6）	18（19.4）	0	1.07	0.30
	CPO组	3（2.1）	40（28.6）	97（69.3）	0.23	0.63

选择文件类型/文献管理软件名称

选择包含的内容