幽门螺杆菌cagL氨基酸多态性与消化性溃疡及胃癌的关系
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摘要
目的探讨幽门螺杆菌cagL氨基酸多态性与消化性溃疡及胃癌的关系。方法选取2015年2月至2016年10月在本院诊治的85例消化性溃疡病患者为消化性溃疡组,另选取同期于本院诊治的90例胃癌患者为胃癌组,选取同期于本院体检的74例健康人员为对照组。三组人员均幽门螺杆菌阳性。采集三组受试人员的胃活检标本提取DNA,经两对引物-聚合酶链式反应(PCR?CTPP)检测幽门螺杆菌cagL氨基酸D58、E59基因多态性,Hardy?weinberg遗传平衡定律验证两组基因型频率是否具有代表性;采用Logistic回归分析cagL氨基酸多态性与胃癌发生风险之间的关系;观察并分析其与胃癌患者临床病理参数的关系。结果 cagL在D58位点存在单核苷酸多态性,分别为野生型纯合子AA型、突变杂合子AG型、突变纯合子GG型;cagL在E59存在单核苷酸多态性,分别为野生型纯合子GG型、突变杂合子AG型、突变纯合子AA型;D58、E59基因多态性基因型频率分布符合Hardy?weinberg定律;与对照组、消化性溃疡组相比,cagL D58、E59位点基因型频率在胃癌组间分布对比差异有统计学意义(P<0.05);与对照组相比,消化性溃疡组cagL D58、E59位点基因型分布差异有统计学意义(P<0.05);Logistic回归分析结果显示胃癌组中cagL D58 AG、GG与cagL E59 AG、AA均为胃癌发生的危险基因型;胃癌患者临床分析结果显示cagL D58、E59基因多态性位点各基因型与患者淋巴结转移、TNM分期及浸润深度显著相关(P<0.05)。结论幽门螺杆菌cagL氨基酸多态性与胃癌及消化性溃疡发病有关,而D58位点GG、AG基因型与E59位点AA、AG基因型可增加胃癌的发病风险。
Objective To explore the relationships between cagL amino acid polymorphism of Helicobacter pylori with peptic ulcer disease and gastric cancer. Methods 85 cases of peptic ulcer disease patients in our hospital from February 2015 to October 2016 were selected as peptic ulcer group,and 90 cases of gastric cancer patients in our hospital were selected as the gastric cancer group;74 healthy people who were in the physical examination at the same time were selected as the control group. Gastric biopsy specimens from three groups of subjects were used to extract DNA;two pairs of primers polymerase chain reaction with confronting two?pair primers(PCR?CTPP)were used to detect the polymorphism of cagL for amino acid D58 and E59 of Helicobacter pylori. The Hardy?weinberg equilibrium of the alleles was analyzed. Logistic regression was used to analyze the relationships between cagL amino acid polymorphism and the risk of gastric cancer and the clinical pathological parameters. Results There were single nucleotide polymorphisms of cagL at D58 loci,which were wild type homozygote AA type,mutant heterozygous AG type and mutant homozygous GG type;there were single nucleotide polymorphisms of cagL in E59,which were wild type homozygote GG type,mutant heterozygous AG type and mutant homozygous AA type. The frequency distribution of D58 and E59 gene polymorphisms was in accordance with Hardy?weinberg′s law. The genotype frequencies of cagL D58 and E59 were significantly different between the control group and gastric cancer groups(P<0.05). Compared with the control group,the genotype distribution of cagL D58 and E59 in the peptic ulcer group was statistically significant(P<0.05). Logistic regression analysis showed that cagL D58 AG,GG and cagL E59 AG,AA in the gastric cancer group were risk genotypes of gastric cancer. The clinical analysis of gastric cancer patients showed that cagL D58 and E59 gene polymorphisms were significantly associated with lymph node metastasis,TNM stage and depth of invasion(P<0.05). Conclusion The cagL amino acid polymorphism of Helicobacter pylori is associated with gastric cancer and peptic ulcers,while the D58 locus GG,AG genotype and E59 loci AA and AG genotypes may increase the risk of gastric cancer.
Objective To explore the relationships between cagL amino acid polymorphism of Helicobacter pylori with peptic ulcer disease and gastric cancer. Methods 85 cases of peptic ulcer disease patients in our hospital from February 2015 to October 2016 were selected as peptic ulcer group,and 90 cases of gastric cancer patients in our hospital were selected as the gastric cancer group;74 healthy people who were in the physical examination at the same time were selected as the control group. Gastric biopsy specimens from three groups of subjects were used to extract DNA;two pairs of primers polymerase chain reaction with confronting two?pair primers(PCR?CTPP)were used to detect the polymorphism of cagL for amino acid D58 and E59 of Helicobacter pylori. The Hardy?weinberg equilibrium of the alleles was analyzed. Logistic regression was used to analyze the relationships between cagL amino acid polymorphism and the risk of gastric cancer and the clinical pathological parameters. Results There were single nucleotide polymorphisms of cagL at D58 loci,which were wild type homozygote AA type,mutant heterozygous AG type and mutant homozygous GG type;there were single nucleotide polymorphisms of cagL in E59,which were wild type homozygote GG type,mutant heterozygous AG type and mutant homozygous AA type. The frequency distribution of D58 and E59 gene polymorphisms was in accordance with Hardy?weinberg′s law. The genotype frequencies of cagL D58 and E59 were significantly different between the control group and gastric cancer groups(P<0.05). Compared with the control group,the genotype distribution of cagL D58 and E59 in the peptic ulcer group was statistically significant(P<0.05). Logistic regression analysis showed that cagL D58 AG,GG and cagL E59 AG,AA in the gastric cancer group were risk genotypes of gastric cancer. The clinical analysis of gastric cancer patients showed that cagL D58 and E59 gene polymorphisms were significantly associated with lymph node metastasis,TNM stage and depth of invasion(P<0.05). Conclusion The cagL amino acid polymorphism of Helicobacter pylori is associated with gastric cancer and peptic ulcers,while the D58 locus GG,AG genotype and E59 loci AA and AG genotypes may increase the risk of gastric cancer.
引文
[1]周春芳,孙泽群,巍刚,等.贞芪扶正胶囊联合抗生素治疗幽门螺杆菌阳性慢性胃炎的探讨[J].中国热带医学,2017,17(7):722-724,727.
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[10]Shahi H,Bahreiny R,Reiisi S.Helicobacter pylori and its virulence factors′effect on serum oxidative DNA damages in adults with dyspepsia[J].Acta Med Iran,2016,54(11):704-708.
[11]Farzi N,Yadegar A,Aghdaei HA,et al.Genetic diversity and functional analysis of oipA gene in association with other virulence factors among Helicobacter pylori isolates from Iranian patients with different gastric diseases[J].Infect Genet Evol,2018,60:26-34.
[12]Koelblen T,BergéC,Cherrier MV,et al.Molecular dissection of protein-protein interactions between integrinα5β1 and the Helicobacter pylori Cag type IV secretion system[J].FEBS J,2017,284(23):4143-4157.
[13]Bonsor DA,Pham KT,Beadenkopf R,et al.Integrin engagement by the helical RGD motif of the Helicobacter pylori CagL protein is regulated by pH-induced displacement of a neighboring helix[J].J Biol Chem,2015,290(20):12929-12940.
[14]Tafreshi M,Zwickel N,Gorrell RJ,et al.Preservation of Helicobacter pylori CagA translocation and host cell proinflammatory responses in the face of CagL hypervariability at amino acid residues 58/59[J].PLoS One,2015,10(7):e0133531.
[15]Valenzuela MA,Canales J,Corvalán AH,et al.Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis[J].World J Gastroenterol,2015,21(45):12742-12756.
[16]Wiedemann T,Hofbaur S,Loell E,et al.A C-terminal CoiledCoil region of CagL is responsible for Helicobacter pylori-induced IL-8 expression[J].Eur J Microbiol Immunol,2016,6(3):186-196.
[17]江海洋,王丽波,范聪聪,等.幽门螺杆菌毒力基因cagA、vacA和iceA与胃十二指肠疾病的关系[J].中国微生态学杂志,2017,29(3):256-260.
[18]韩璐,李欣,吴义琴.黄芪建中汤合温针灸治疗脾胃虚寒型慢性萎缩性胃炎40例[J].中国临床研究,2017,30(12):1697-1698,1701.
[2]Kasai C,Sugimoto K,Moritani L,et al.Changes in plasma ghrelin and leptin levels in patients with peptic ulcer and gastritis following eradication of Helicobacter pylori infection[J].BMC Gastroenterol,2016,16(1):119.
[3]Ogawa H,Iwamoto A,Tanahashi T,et al.Genetic variants of Helicobacter pylori type IV secretion system components CagLand CagI and their association with clinical outcomes[J].Gut Pathog,2017,9:21.
[4]Gorrell RJ,Zwickel N,Reynolds J,et al.Helicobacter pylori CagL hypervariable motif:A global analysis of geographical diversity and association with gastric cancer[J].J Infect Dis,2016,213(12):1927-1931.
[5]中华消化杂志编委会.消化性溃疡诊断与治疗规范(2016年,西安)[J].中华消化杂志,2016,36(8):508-513.
[6]朱锦涛,魏哲威,周志军,等.幽门螺杆菌对胃癌患者预后的影响[J].热带医学杂志,2017,17(5):578-582.
[7]Alarid-Escudero F,Enns EA,MacLehose RF,et al.Force of infection of Helicobacter pylori in Mexico:evidence from a national survey using a hierarchical Bayesian model-corrigendum[J].Epidemiol Infect,2018,146(8):1070.
[8]周凯,徐霖,袁磊,等.海参提取物TBL-12对胃癌HGC-27细胞增殖、迁移、侵袭和凋亡的影响[J].热带医学杂志,2018,18(3):302-306,420.
[9]Khatoon J,Prasad KN,Prakash Rai R,et al.Association of heterogenicity of Helicobacter pylori cag pathogenicity island with peptic ulcer diseases and gastric cancer[J].Br J Biomed Sci,2017,74(3):121-126.
[10]Shahi H,Bahreiny R,Reiisi S.Helicobacter pylori and its virulence factors′effect on serum oxidative DNA damages in adults with dyspepsia[J].Acta Med Iran,2016,54(11):704-708.
[11]Farzi N,Yadegar A,Aghdaei HA,et al.Genetic diversity and functional analysis of oipA gene in association with other virulence factors among Helicobacter pylori isolates from Iranian patients with different gastric diseases[J].Infect Genet Evol,2018,60:26-34.
[12]Koelblen T,BergéC,Cherrier MV,et al.Molecular dissection of protein-protein interactions between integrinα5β1 and the Helicobacter pylori Cag type IV secretion system[J].FEBS J,2017,284(23):4143-4157.
[13]Bonsor DA,Pham KT,Beadenkopf R,et al.Integrin engagement by the helical RGD motif of the Helicobacter pylori CagL protein is regulated by pH-induced displacement of a neighboring helix[J].J Biol Chem,2015,290(20):12929-12940.
[14]Tafreshi M,Zwickel N,Gorrell RJ,et al.Preservation of Helicobacter pylori CagA translocation and host cell proinflammatory responses in the face of CagL hypervariability at amino acid residues 58/59[J].PLoS One,2015,10(7):e0133531.
[15]Valenzuela MA,Canales J,Corvalán AH,et al.Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis[J].World J Gastroenterol,2015,21(45):12742-12756.
[16]Wiedemann T,Hofbaur S,Loell E,et al.A C-terminal CoiledCoil region of CagL is responsible for Helicobacter pylori-induced IL-8 expression[J].Eur J Microbiol Immunol,2016,6(3):186-196.
[17]江海洋,王丽波,范聪聪,等.幽门螺杆菌毒力基因cagA、vacA和iceA与胃十二指肠疾病的关系[J].中国微生态学杂志,2017,29(3):256-260.
[18]韩璐,李欣,吴义琴.黄芪建中汤合温针灸治疗脾胃虚寒型慢性萎缩性胃炎40例[J].中国临床研究,2017,30(12):1697-1698,1701.