Kocak Banu Tufan, Saribas Suat, Demiryas Suleyman, Yilmaz Erkan, Uysal Omer, Kepil Nuray, Demirci Mehmet, Dınc Harika Oyku, Akkus Seher, Gülergün Reyhan, Gareayaghi Nesrin, Dağdeviren Hüseyin Emre, Ozbey Dogukan, Dağ Hamit Harun, Tokman Hrisi Bahar, Tasci Ihsan, Kocazeybek Bekir
T.C. Health Ministry Erenkoy Mental Health, Neurology Training and Research Hospital, Istanbul, Turkey.
Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey.
Infect Genet Evol. 2020 Aug;82:104288. doi: 10.1016/j.meegid.2020.104288. Epub 2020 Mar 13.
Colonization of the human gastric mucosa by H. pylori may cause peptic and duodenal ulcers (DUs), gastric lymphomas, and gastric cancers. The cagL gene is a component of cag T4SS and is involved in cagA translocation into host. An association between the risk of gastric cancer and the type of HLA class II (DR and/or DQ) was suggested in different populations. The aim of this study was to investigate, the clinical association of the cagL gene with host HLA alleles in H. pylori strains that were isolated from patients with gastric cancer, DU, and non-ulcer dyspepsia (NUD) and to determine the HLA allele that confers susceptibility or resistance for the risk of gastric cancer and DU development in Turkish patients. A total of 94 patients (44 gastric cancer and 50 DU patients; 58 male, 36 female; mean age, 49.6 years), and 86 individuals (50 NUD patients and 36 persons with normal gastrointestinal system [NGIS]; 30 male, 56 female; mean age, 47.3 years) were included as the patient and the control groups, respectively. CagA and cagL were determined by PCR method. DNA from peripheral blood samples was obtained by EZ-DNA extraction kit. For HLA SSO typing, LIFECODES SSO Typing kits (HLA-A, HLA-B HLA-C, HLA-DRB1 and HLA-DQA1/B1 kits) were used. The CagL/CagA positivity distribution in the groups were as follows: 42 (95.4%) gastric cancer, 46 (92%) DU and, 34 (68%) NUD and no NGIS cases. The HLA-DQA101 (OR: 3.82) allele was significantly different, suggesting that these individuals with H. pylori strains harbouring the CagL/CagA positivity are susceptible to the risk of gastric cancer and DU, and the HLA-DQA105 (OR, 0.318) allele was suggested as a protective allele for the risk of gastric cancer and DU using univariate analyses. HLA-DQA101 (OR, 2.21), HLA-DQB106 (OR, 2.67), sex (male, OR, 2.27), and CagL/CagA/(<2) EPIYA C repeats (OR, 5.72) were detected independent risk factors that increased the risk of gastric cancer and DU using multivariate analyses. However, the HLA-DRB1*04 (OR, 0.28) allele was shown to be a protective allele, which decreased the risk of gastric cancer and DU. Gastric pathologies result from an interaction between bacterial virulence factors, host epigenetic and environmental factors, and H. pylori strain heterogeneity, such as genotypic variation among strains and variations in H. pylori populations within an individual host.
幽门螺杆菌在人胃黏膜的定植可能会导致消化性溃疡和十二指肠溃疡（DU）、胃淋巴瘤以及胃癌。cagL基因是cag T4SS的一个组成部分，参与cagA转运至宿主细胞。在不同人群中，胃癌风险与II类人类白细胞抗原（DR和/或DQ）类型之间存在关联。本研究的目的是调查从胃癌、DU和非溃疡性消化不良（NUD）患者中分离出的幽门螺杆菌菌株中cagL基因与宿主HLA等位基因的临床关联，并确定赋予土耳其患者胃癌和DU发生易感性或抗性的HLA等位基因。分别纳入94例患者（44例胃癌患者和50例DU患者；58例男性，36例女性；平均年龄49.6岁）和86名个体（50例NUD患者和36例胃肠道系统正常[NGIS]者；30例男性，56例女性；平均年龄47.3岁）作为患者组和对照组。通过PCR方法检测CagA和cagL。使用EZ-DNA提取试剂盒从外周血样本中获取DNA。对于HLA SSO分型，使用LIFECODES SSO分型试剂盒（HLA-A、HLA-B、HLA-C、HLA-DRB1和HLA-DQA1/B1试剂盒）。各组中CagL/CagA阳性分布如下：42例（95.4%）胃癌患者、46例（92%）DU患者、34例（68%）NUD患者，且无NGIS病例。HLA-DQA101（比值比：3.82）等位基因有显著差异，表明携带CagL/CagA阳性幽门螺杆菌菌株的个体易患胃癌和DU风险，单因素分析表明HLA-DQA105（比值比，0.318）等位基因是胃癌和DU风险的保护等位基因。多因素分析检测到HLA-DQA101（比值比，2.21）、HLA-DQB106（比值比，2.67）、性别（男性，比值比，2.27）和CagL/CagA/（<2）EPIYA C重复序列（比值比，5.72）是增加胃癌和DU风险的独立危险因素。然而，HLA-DRB1*04（比值比，0.28）等位基因显示为保护等位基因，可降低胃癌和DU风险。胃部病变是由细菌毒力因子、宿主表观遗传和环境因素以及幽门螺杆菌菌株异质性（如菌株间的基因型变异和个体宿主体内幽门螺杆菌群体的变异）之间的相互作用导致的。
