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Genetic diversity and amino acid sequence polymorphism in Helicobacter pylori CagL hypervariable motif and its association with virulence markers and gastroduodenal diseases

机译:幽门螺杆菌CagL高变基序的遗传多样性和氨基酸序列多态性及其与毒力标记和胃十二指肠疾病的关系

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Genetic variability in cagL gene especially within the Helicobacter?pylori CagL hypervariable motif (CagLHM) may affect the development of gastric cancer. Therefore, this study was conducted to investigate the association of CagL diversity with clinical outcomes and with H?pylori virulence markers. A total of 126 patients with different gastric diseases including non‐ulcer dyspepsia (NUD), peptic ulcer disease (PUD), gastric erosion (GE), and gastric cancer (GC) were enrolled. H?pylori was cultured from gastric biopsies, and the isolates were screened for the presence of cagL , cagA , vacA , babA2 , sabA , and cag PAI integrity by PCR. The amino acid polymorphisms of cagL were analyzed using DNA sequencing. We isolated 61 (48.4%) H?pylori strains from 36 NUD, eight PUD, 12 GE, and five GC patients. Almost all isolates were cagL positive (97%), and their RGD, RHS, and SKIIVK motifs were highly conserved. Among 10 CagLHM variants identified, NEIGQ and NKIGQ were detected as the most prevalent sequences. Interestingly, a significant association was found between the presence of NKMGK and PUD ( P ?=?0.002). Notably, the NEIGQ isolates with multiple C‐type EPIYA repeat that carried intact cag PAI correlated with disease risk for PUD, GE, and GC ( P ?=?0.021). In conclusion, we identified novel variants of H?pylori CagLHM sequences in Iranian population such as NKMGK, which was associated with disease risk for PUD. Further studies using a large number of strains are required to better clarify the function of certain CagLHM motifs in gastric carcinogenesis and disease outcome.
机译:cagL基因的遗传变异,尤其是幽门螺杆菌CagL高变基序(CagLHM)可能影响胃癌的发展。因此,本研究旨在研究CagL多样性与临床结果和幽门螺杆菌毒力标记物的关系。总共纳入了126名患有不同胃病的患者,包括非溃疡性消化不良(NUD),消化性溃疡病(PUD),胃糜烂(GE)和胃癌(GC)。从胃活检物中培养幽门螺杆菌,并通过PCR筛选分离物是否存在cagL,cagA,vacA,babA2,sabA和cag PAI完整性。使用DNA测序分析cagL的氨基酸多态性。我们从36名NUD,8名PUD,12名GE和5名GC患者中分离出61株(48.4%)幽门螺杆菌菌株。几乎所有分离株均为cagL阳性(97%),它们的RGD,RHS和SKIIVK基序是高度保守的。在鉴定出的10个CagLHM变体中,NEIGQ和NKIGQ被检测为最普遍的序列。有趣的是,在NKMGK和PUD的存在之间发现了显着的相关性(P = 0.002)。值得注意的是,带有多个C型EPIYA重复序列的NEIGQ分离株携带完整的cag PAI与PUD,GE和GC的疾病风险相关(P == 0.021)。总之,我们在伊朗人群中鉴定了H?pylori CagLHM序列的新变异体,例如NKMGK,这与PUD的疾病风险有关。需要使用大量菌株进行进一步研究,以更好地阐明某些CagLHM基序在胃癌发生和疾病预后中的功能。

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