ITGA1基因多态性与幽门螺杆菌感染的关联性分析
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摘要
目的:探讨整联蛋白α亚基1 (ITGA1)基因单核苷酸多态性(SNP)与幽门螺杆菌感染的关联性,为幽门螺杆菌感染相关疾病的防治提供依据。方法:选择体检者281人的血液样本,采用ELISA法确定体验者血液中幽门螺杆菌的感染状况,根据抗体滴度将样本分为幽门螺杆菌阴性组(n=159)和幽门螺杆菌阳性组(n=122)。采用TaqMan法对ITGA1基因的rs1862610、rs2432143和rs2447867位点进行基因分型,采用Haploview 4.0软件构建单体型,采用非条件性Logistic回归检测各等位基因、基因型的SNPs和单体型与幽门螺杆菌感染的关系。结果:ITGA1基因rs1862610和rs2432143位点的SNPs与幽门螺杆菌感染无关联(P>0.05);ITGA1基因rs2447867位点的SNP与幽门螺杆菌感染有关联(P<0.05),携带基因型CT可降低幽门螺杆菌感染风险(CTvs CC:OR=0.52,95%CI:0.31~0.86)。ITGA1基因rs1862610和rs2432143位点SNPs之间存在强连锁不平衡(D’=1),构成单体型块,各单体型与幽门螺杆菌感染无关联(P>0.05)。结论:ITGA1基因rs2447867位点的SNP与幽门螺杆菌感染有关联,携带基因型CT可降低幽门螺杆菌感染风险。
Objective:To investigate the association between single nucleotide polymorphism(SNP)of integrinα-subunit 1(ITGA1)gene and Helicobacter pylori(H.pylori)infection,and to provide the basis for the prevention and treatment of H.pylori infection-related diseases.Methods:The blood samples of 281 examinees were detected.ELISA method was used to confirm the status of H.pylori infection in the blood of the examinees.The samples were divided into H.pylori negative group(n=159)and H.pylori positive group(n=122)according to the antibody titers.The genotypes of rs1862610,rs2432143,and rs2447867 sites in ITGA1 gene were detected by TaqMan method.The haplotype was constructed by Haploview software 4.0 and unconditional Logistic regression was used to evaluate the associations between the SNPs of alleles,genotypes and haplotypes and H.pylori infection.Results:The SNPs of rs1862610 and rs2432143 sites in ITGA1 gene were not associated with H.pylori infection(P>0.05).The SNPs of rs2447867 site in ITGA1 gene was significantly associated with H.pylori infection(P<0.05).Carrying CT genotype decreased the risk of H.pyloriinfection(CTvs CC:OR=0.52,95% CI:0.31-0.86).The SNPs between rs1862610 and rs2432143 sites in ITGA1 gene had a strong linkage disequilibrium(D′=1)and formed a block.None of the haplotypes was associated with H.pylori infection(P>0.05).Conclusion:The SNP of rs2447867 site in ITGA1 gene is associated with H.pylori infection,and carrying CT genotype can decrease the risk of H.pylori infection.
Objective:To investigate the association between single nucleotide polymorphism(SNP)of integrinα-subunit 1(ITGA1)gene and Helicobacter pylori(H.pylori)infection,and to provide the basis for the prevention and treatment of H.pylori infection-related diseases.Methods:The blood samples of 281 examinees were detected.ELISA method was used to confirm the status of H.pylori infection in the blood of the examinees.The samples were divided into H.pylori negative group(n=159)and H.pylori positive group(n=122)according to the antibody titers.The genotypes of rs1862610,rs2432143,and rs2447867 sites in ITGA1 gene were detected by TaqMan method.The haplotype was constructed by Haploview software 4.0 and unconditional Logistic regression was used to evaluate the associations between the SNPs of alleles,genotypes and haplotypes and H.pylori infection.Results:The SNPs of rs1862610 and rs2432143 sites in ITGA1 gene were not associated with H.pylori infection(P>0.05).The SNPs of rs2447867 site in ITGA1 gene was significantly associated with H.pylori infection(P<0.05).Carrying CT genotype decreased the risk of H.pyloriinfection(CTvs CC:OR=0.52,95% CI:0.31-0.86).The SNPs between rs1862610 and rs2432143 sites in ITGA1 gene had a strong linkage disequilibrium(D′=1)and formed a block.None of the haplotypes was associated with H.pylori infection(P>0.05).Conclusion:The SNP of rs2447867 site in ITGA1 gene is associated with H.pylori infection,and carrying CT genotype can decrease the risk of H.pylori infection.
引文
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[16] Wu XW,Ji HZ, Yang MF,et al. Helicobacter pylori infection and inflammatory bowel disease in Asians:a metaanalysis[J].World J Gastroenterol,2015,21(15):4750-4756.
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[18]Nieberler M,Reuning U,Reichart F,et al.Exploring the role of RGD-recognizing integrins in cancer[J].Cancers,2017,9(12):116.
[19]Backert S,Tegtmeyer N. Type IV secretion and signal transduction of Helicobacter pylori cagA through interactions with host cell receptors[J].Toxins,2017,9(4):115.
[20]Servetas SL,Bridge DR,Merrell DS.Molecular mechanisms of gastric cancer initiation and progression by Helicobacter pylori[J].Curr Opin Infect Dis,2016,29(3):304-310.
[21]Fukuda K,Saikawa Y,Yagi H,et al.Role of integrinα1subunitsingastriccancerpatientswithperitoneal dissemination[J].Mol Med Rep,2012,5(2):336-340.
[22]Yim DH,Zhang YW,Eom SY,et al.ITGA1polymorphisms and haplotypes are associated with gastric cancer risk in a Korean population[J]. World J Gastroenterol, 2013,19(35):5870-5876.
[2] Díaz P, Valenzuela Valderrama M, Bravo J, et al.Helicobacter pylori and gastric cancer:adaptive cellular mechanisms involved in disease progression[J]. Front Microbiol,2018,9:5.
[3] Compare D,Rocco A,Nardone G.Risk factors in gastric cancer[J].Eur Rev Med Pharmacol Sci,2010,14(4):302-308.
[4] Polk DB,Peek RM Jr.Helicobacter pylori:gastric cancer and beyond[J].Nat Rev Cancer,2010,10(6):403-414.
[5] Huang Y,Wang QL,Cheng DD,et al.Adhesion and invasion of gastric mucosa epithelial cells by Helicobacter pylori[J].Front Cell Infect Microbiol,2016,6:159.
[6] Xiang W,Shi JF,Li P,et al.Estimation of cancer cases and deaths attributable to infection in China[J].Cancer Causes Control,2011,22(8):1153-1161.
[7] Mayerle J,den Hoed CM,Schurmann C,et al.Identification of genetic loci associated with Helicobacter pylori serologic status[J].JAMA,2013,309(18):1912-1920.
[8] Zheng Z,Jia Y,Hou L,et al.Genetic variation inα4GnT in relation to Helicobacter pylori serology and gastric cancer risk[J].Helicobacter,2009,14(5):120-125.
[9] Yim DH,Zhang YW,Eom SY,et al.ITGA1polymorphisms and haplotypes are associated with gastric cancer risk in a Korean population[J]. World J Gastroenterol,2013,19(35):5870-5876.
[10]Fukuda K,Saikawa Y,Yagi H,et al.Role of integrinα1subunitsingastriccancerpatientswithperitoneal dissemination[J].Mol Med Rep,2012,5(2):336-340.
[11]Kosaka N.Decoding the secret of cancer by means of extracellular vesicles[J].J Clin Med,2016,5(2):pii:E22.
[12]Zhou CJ,Zhang LW, Gao F,et al. Common genetic variations in the MUC5AC gene are not related to helicobacter pylori serologic status[J].Asian Pac J Cancer Prev,2014,15(24):10719-10722.
[13]高芳,秦金东,李晶晶,等.包头地区汉族人群COX-2基因多态性与幽门螺杆菌感染的关系[J].中国卫生检验杂志,2015,25(2):220-222.
[14]Oluwasola AO.Genetic determinants and clinico-pathological outcomes of helicobacter pylori infection[J].Ann Ib Postgrad Med,2014,12(1):22-30.
[15]Dadashzadeh K,Peppelenbosch MP,Adamu AI.Helicobacter pylori pathogenicity factors related to gastric cancer[J].Can J Gastroenterol Hepatol,2017,2017:7942489.
[16] Wu XW,Ji HZ, Yang MF,et al. Helicobacter pylori infection and inflammatory bowel disease in Asians:a metaanalysis[J].World J Gastroenterol,2015,21(15):4750-4756.
[17]NiccoliAsabella A,Di Palo A,Altini C,et al.Multimodality imagingintumorangiogenesis:presentstatusand perspectives[J].Int J Mol Sci,2017,18(9).pii:E1864.
[18]Nieberler M,Reuning U,Reichart F,et al.Exploring the role of RGD-recognizing integrins in cancer[J].Cancers,2017,9(12):116.
[19]Backert S,Tegtmeyer N. Type IV secretion and signal transduction of Helicobacter pylori cagA through interactions with host cell receptors[J].Toxins,2017,9(4):115.
[20]Servetas SL,Bridge DR,Merrell DS.Molecular mechanisms of gastric cancer initiation and progression by Helicobacter pylori[J].Curr Opin Infect Dis,2016,29(3):304-310.
[21]Fukuda K,Saikawa Y,Yagi H,et al.Role of integrinα1subunitsingastriccancerpatientswithperitoneal dissemination[J].Mol Med Rep,2012,5(2):336-340.
[22]Yim DH,Zhang YW,Eom SY,et al.ITGA1polymorphisms and haplotypes are associated with gastric cancer risk in a Korean population[J]. World J Gastroenterol, 2013,19(35):5870-5876.