Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
PLoS One. 2024 Sep 9;19(9):e0309844. doi: 10.1371/journal.pone.0309844. eCollection 2024.
Helicobacter pylori (H. pylori) virulence factors, particularly the cagA and vacA genotypes, play important roles in the pathogenic process of gastrointestinal disease.
The cagA and vacA genotypes of 87 H. pylori strains were determined by PCR and sequencing. The EPIYA and CM motif patterns were analyzed and related to clinical outcomes. We examined the associations between the virulence genes of H. pylori and gastrointestinal diseases in Shandong, and the results were analyzed via the chi-square test and logistic regression model.
Overall, 76 (87.36%) of the strains carried the East Asian-type CagA, with the ABD types being the most prevalent (90.79%). However, no significant differences were observed among the different clinical outcomes. The analysis of CagA sequence types revealed 8 distinct types, encompassing 250 EPIYA motifs, including 4 types of EPIYA or EPIYA-like sequences. Additionally, 28 CM motifs were identified, with the most prevalent patterns being E (66.67%), D (16.09%), and W-W (5.75%). Notably, a significant association was discovered between strains with GC and the CM motif pattern D (P < 0.01). With respect to the vacA genotypes, the strains were identified as s1, s2, m1, m2, i1, i2, d1, d2, c1, and c2 in 87 (100%), 0 (0), 26 (29.89%), 61 (70.11%), 73 (83.91%), 14 (16.09%), 76 (87.36%), 11 (12.64%), 18 (20.69%), and 69 (79.31%), respectively. Specifically, the vacA m1 and c1 genotypes presented a significantly greater prevalence in strains from GC compared to CG (P < 0.05). Following adjustment for age and sex, the vacA c1 genotype demonstrated a notable association with GC (OR = 5.174; 95% CI, 1.402-20.810; P = 0.012). This association was both independent of and more pronounced than the correlations between vacA m1 and GC.
CagA proteins possessing CM motif pattern D were more frequently observed in patients with GC (P < 0.01), implying a potentially higher virulence of CM motif pattern D than the other CM motif patterns. Moreover, a strong positive association was identified between the vacA c1 genotype and GC, indicating that the vacA c1 genotype is a robust risk indicator for GC among male patients aged ≥55 years in Shandong.
幽门螺杆菌（H. pylori）的毒力因子，尤其是 cagA 和 vacA 基因型，在胃肠道疾病的发病机制中起着重要作用。
通过 PCR 和测序检测 87 株 H. pylori 菌株的 cagA 和 vacA 基因型。分析 EPIYA 和 CM 基序模式，并将其与临床结果相关联。我们检测了 H. pylori 毒力基因与山东地区胃肠道疾病的相关性，并通过卡方检验和 logistic 回归模型进行了分析。
总体而言，76（87.36%）株携带东亚型 CagA，其中 ABD 型最为常见（90.79%）。然而，不同临床结果之间没有显著差异。CagA 序列类型分析显示 8 种不同类型，包含 250 个 EPIYA 基序，包括 4 种 EPIYA 或 EPIYA 样序列。此外，还鉴定出 28 种 CM 基序模式，其中最常见的模式为 E（66.67%）、D（16.09%）和 W-W（5.75%）。值得注意的是，GC 菌株与 CM 基序模式 D 之间存在显著关联（P < 0.01）。关于 vacA 基因型，87 株菌中分别鉴定为 s1、s2、m1、m2、i1、i2、d1、d2、c1 和 c2，分别为 87.36%、0%、29.89%、70.11%、83.91%、16.09%、76.87%、12.64%、20.69%和 79.31%。具体而言，与 CG 相比，GC 中 vacA m1 和 c1 基因型的患病率显著更高（P < 0.05）。在调整年龄和性别后，vacA c1 基因型与 GC 之间存在显著关联（OR = 5.174；95%CI，1.402-20.810；P = 0.012）。这种关联既独立于 vacA m1 与 GC 之间的相关性，也比其更为显著。
CM 基序模式 D 的 CagA 蛋白在 GC 患者中更为常见（P < 0.01），这表明 CM 基序模式 D 的毒力可能高于其他 CM 基序模式。此外，vacA c1 基因型与 GC 之间存在强烈的正相关关系，表明在山东地区，≥55 岁男性患者中，vacA c1 基因型是 GC 的一个强有力的风险指标。
