Department of Medical Genetics, University of Medicine and Pharmacy, Hue University, 6, Ngo Quyen Street, Hue City, 49100, Vietnam.
Department of Internal Medicine, University of Medicine and Pharmacy, Hue University, Hue City, Vietnam.
Braz J Microbiol. 2024 Jun;55(2):1393-1404. doi: 10.1007/s42770-024-01328-8. Epub 2024 Apr 27.
Helicobacter pylori is the most common cause of gastroduodenal diseases. The concept that cagA-positive H. pylori is a risk factor for gastric cancer appears to be true only for H. pylori strains from Western countries. Other virulent genes may have a synergistic interaction with cagA during pathogenesis. This study aims to investigate H. pylori cagA, vacA, and iceA prevalence, genotypes, and their association to clinical outcomes in Vietnamese patients. The cagA status and vacA and iceA genotypes were determined using the PCR technique on DNA extracted from gastric biopsies of 141 patients with gastroduodenal diseases. After performing molecular analysis for cagA, vacA, and iceA genes, samples with mixed H. pylori strains, positivity, or negativity for both cagA and cagPAI-empty site, or unidentified genotypes were excluded. Finally, 107 samples were examined. The presence of the cagA, vacA, and iceA genes were detected in 77.6%, 100%, and 80.4% of cases, respectively. Notably, cagA( +) with EPIYA-ABD, vacA s1i1m1, vacA s1i1m2, iceA1, and iceA2 accounted for 73.8%, 44.9%, 33.6%, 48.6%, and 31.8% of cases, respectively. Four iceA2 subtypes (24-aa, 59-aa, 94-aa, and 129-aa variants) were found, with the 59-aa variant the most prevalent (70.6%). The cagA( +)/vacAs1i1m1/iceA1 and cagA( +)/vacAs1i1m2/iceA1 combinations were found in 26.2% and 25.1% of cases, respectively. A multivariable logistic regression analysis was performed, after adjusting for age and gender, with the gastritis group was used as a reference control. Statistically significant associations were found between the vacA s1i1m2 genotype, the iceA1 variant, and the cagA( +)/vacAs1i1m2/iceA1 combination and gastric cancer; the adjusted ORs were estimated as 18.02 (95% CI: 3.39-95.81), 4.09 (95% CI: 1.1-15.08), and 16.19 (95% CI: 3.42-76.66), respectively. Interestingly, for the first time, our study found that vacA s1i1m2, but not vacA s1i1m1, was a risk factor for gastric cancer. This study illustrates the genetic diversity of the H. pylori cagA, vacA, and iceA genes across geographical regions and contributes to understanding the importance of these genotypes for clinical outcomes.
幽门螺杆菌是导致胃十二指肠疾病的最常见原因。CagA 阳性幽门螺杆菌是胃癌危险因素的概念似乎仅适用于西方国家的幽门螺杆菌菌株。其他毒力基因可能在发病机制中与 CagA 具有协同作用。本研究旨在调查越南患者中幽门螺杆菌 cagA、vacA 和 iceA 的流行率、基因型及其与临床结果的关系。使用聚合酶链反应技术，从 141 例胃十二指肠疾病患者的胃活检组织中提取 DNA，检测 cagA 状态和 vacA 和 iceA 基因型。对 cagA、vacA 和 iceA 基因进行分子分析后，排除了混合幽门螺杆菌菌株、cagA 和 cagPAI-空位点阳性或阴性以及无法识别基因型的样本。最后，检查了 107 个样本。分别在 77.6%、100%和 80.4%的病例中检测到 cagA、vacA 和 iceA 基因的存在。值得注意的是，cagA(+)伴有 EPIYA-ABD、vacA s1i1m1、vacA s1i1m2、iceA1 和 iceA2 分别占 73.8%、44.9%、33.6%、48.6%和 31.8%。发现了四种 iceA2 亚型（24-aa、59-aa、94-aa 和 129-aa 变体），其中 59-aa 变体最为常见（70.6%）。cagA(+) / vacAs1i1m1 / iceA1 和 cagA(+) / vacAs1i1m2 / iceA1 组合分别在 26.2%和 25.1%的病例中发现。在调整年龄和性别后，进行了多变量逻辑回归分析，以胃炎组为参考对照。发现 vacA s1i1m2 基因型、iceA1 变体以及 cagA(+) / vacAs1i1m2 / iceA1 组合与胃癌之间存在统计学显著关联；调整后的 OR 估计值分别为 18.02（95%CI：3.39-95.81）、4.09（95%CI：1.1-15.08）和 16.19（95%CI：3.42-76.66）。有趣的是，本研究首次发现 vacA s1i1m2 而不是 vacA s1i1m1 是胃癌的危险因素。本研究说明了幽门螺杆菌 cagA、vacA 和 iceA 基因在地理区域上的遗传多样性，并有助于了解这些基因型对临床结果的重要性。
