胃十二指肠病变与幽门螺杆菌 cagL（细胞毒素相关基因 L）多态性的关系。

The Relationship between Gastroduodenal Pathologies and Helicobacter pylori cagL (Cytotoxin-Associated Gene L) Polymorphism.

机构信息

Department of Medical Microbiology, İstanbul University Cerrahpaşa Faculty of Medicine, İstanbul, Turkey.

Department of General Surgery, İstanbul University Cerrahpaşa Faculty of Medicine, İstanbul, Turkey.

出版信息

Turk J Gastroenterol. 2023 Apr;34(4):346-355. doi: 10.5152/tjg.2023.22274.

DOI:10.5152/tjg.2023.22274

PMID:36789984

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10210604/

Abstract

BACKGROUND

The polymorphisms in the region between 58 and 62 amino acids of the 194-amino acid CagL protein (CagL hypervariable motif) affect the binding affinity of CagL to integrin α5β1 (ITGA5B1) receptor in host epithelial cells and have an effect on the development of various gastrointestinal diseases. We aimed to evaluate the associations of gastroduodenal pathologies, with the polymorphisms of cagL gene of Helicobacter pylori (H. pylori) and also associations between vacA genotypes and cagL polymorphisms.

METHODS

A total of 19 gastric cancer, 16 duodenal ulcer, and 26 non-ulcer dyspepsia patients were included in this case-control study. All cases had H. pylori. A fragment of 651 bp from gene cagL (hp0539) and cagA, vacA genes was amplified by polymerase chain reaction. Purified polymerase chain reaction products were sequenced by Sanger sequencing, and nucleotide sequences were translated into amino acid sequences.

RESULTS

All of the H. pylori strains had cagL and cagA genes. In the 16 (84%) gastric cancer cases, the D58 amino acid polymorphism was significant than the 4 (15.4%) duodenal ulcer cases (P = .029), and the D58/K59 amino acid polymorphism was significant in 12 (63.1%) of the gastric cancer cases than 1 (3.85%) duodenal ulcer case (P = .008). D58/K59 and DKIGQ (n = 10; 52.63%) were the most common polymorphisms in the gastric cancer and were associated with the vacA genotype s1/m2, respectively (P = .022 and P = .008). The D58/K59 amino acid polymorphism was found to have a significant Odds Ratio (OR) value of 8.9 (P = .0017) in multivariate logistic regression analysis.

CONCLUSIONS

The risk of gastric cancer development is 8.9 times higher with D58/K59 polymorphism.

摘要

背景

CagL 蛋白（CagL 高变区）194 个氨基酸中 58-62 位氨基酸的多态性影响 CagL 与宿主上皮细胞整合素 α5β1（ITGA5B1）受体的结合亲和力，对各种胃肠道疾病的发展有影响。本研究旨在评估胃十二指肠病变与幽门螺杆菌（H. pylori）cagL 基因多态性的关系，以及 vacA 基因型与 cagL 多态性的关系。

方法

本病例对照研究共纳入 19 例胃癌、16 例十二指肠溃疡和 26 例非溃疡性消化不良患者。所有病例均感染 H. pylori。采用聚合酶链反应（PCR）扩增 cagL（hp0539）和 cagA、vacA 基因的 651bp 片段。通过 Sanger 测序法对纯化的 PCR 产物进行测序，将核苷酸序列翻译成氨基酸序列。

结果

所有 H. pylori 株均携带 cagL 和 cagA 基因。在 16 例（84%）胃癌病例中，D58 氨基酸多态性显著高于 4 例（15.4%）十二指肠溃疡病例（P=0.029），D58/K59 氨基酸多态性在 12 例（63.1%）胃癌病例中显著高于 1 例（3.85%）十二指肠溃疡病例（P=0.008）。D58/K59 和 DKIGQ（n=10；52.63%）是胃癌中最常见的多态性，分别与 vacA 基因型 s1/m2 相关（P=0.022 和 P=0.008）。在多变量逻辑回归分析中，D58/K59 氨基酸多态性的优势比（OR）值为 8.9（P=0.0017）。