幽门螺杆菌CagA中的EPIYA-ABCC基序模式与墨西哥人群的消化性溃疡和胃癌有关。
The EPIYA-ABCC motif pattern in CagA of Helicobacter pylori is associated with peptic ulcer and gastric cancer in Mexican population.
作者信息
Beltrán-Anaya Fredy Omar, Poblete Tomás Manuel, Román-Román Adolfo, Reyes Salomón, de Sampedro José, Peralta-Zaragoza Oscar, Rodríguez Miguel Ángel, del Moral-Hernández Oscar, Illades-Aguiar Berenice, Fernández-Tilapa Gloria
出版信息
BMC Gastroenterol. 2014 Dec 24;14:223. doi: 10.1186/s12876-014-0223-9.
BACKGROUND
Helicobacter pylori chronic infection is associated with chronic gastritis, peptic ulcer, and gastric cancer. Cytotoxin-associated gene A (cagA)-positive H. pylori strains increase the risk of gastric pathology. The carcinogenic potential of CagA is linked to its polymorphic EPIYA motif variants. The goals of this study were to investigate the frequency of cagA-positive Helicobacter pylori in Mexican patients with gastric pathologies and to assess the association of cagA EPIYA motif patterns with peptic ulcer and gastric cancer.
METHODS
A total of 499 patients were studied; of these, 402 had chronic gastritis, 77 had peptic ulcer, and 20 had gastric cancer. H. pylori DNA, cagA, and the EPIYA motifs were detected in total DNA from gastric biopsies by PCR. The type and number of EPIYA segments were determined by the electrophoretic patterns. To confirm the PCR results, 20 amplicons of the cagA 3' variable region were sequenced, and analyzed in silico, and the amino acid sequence was predicted with MEGA software, version 5. The odds ratio (OR) was calculated to determine the associations between the EPIYA motif type and gastric pathology and between the number of EPIYA-C segments and peptic ulcers and gastric cancer.
RESULTS
H. pylori DNA was found in 287 (57.5%) of the 499 patients, and 214 (74%) of these patients were cagA-positive. The frequency of cagA-positive H. pylori was 74.6% (164/220) in chronic gastritis patients, 73.6% (39/53) in peptic ulcer patients, and 78.6% (11/14) in gastric cancer patients. The EPIYA-ABC pattern was more frequently observed in chronic gastritis patients (79.3%, 130/164), while the EPIYA-ABCC sequence was more frequently observed in peptic ulcer (64.1%, 25/39) and gastric cancer patients (54.5%, 6/11). However, the risks of peptic ulcer (OR = 7.0, 95% CI = 3.3-15.1; p < 0.001) and gastric cancer (OR = 5.9, 95% CI = 1.5-22.1) were significantly increased in individuals who harbored the EPIYA-ABCC cagA gene pattern.
CONCLUSIONS
cagA-positive H. pylori is highly prevalent in southern Mexico, and all CagA variants were of the western type. The cagA alleles that code for EPIYA-ABCC motif patterns are associated with peptic ulcers and gastric cancer.
背景
幽门螺杆菌慢性感染与慢性胃炎、消化性溃疡及胃癌相关。细胞毒素相关基因A（cagA）阳性的幽门螺杆菌菌株会增加胃部病变风险。CagA的致癌潜力与其多态性EPIYA基序变体有关。本研究的目的是调查墨西哥胃部病变患者中cagA阳性幽门螺杆菌的频率，并评估cagA EPIYA基序模式与消化性溃疡和胃癌的关联。
方法
共研究了499例患者；其中，402例患有慢性胃炎，77例患有消化性溃疡，20例患有胃癌。通过聚合酶链反应（PCR）在胃活检组织的总DNA中检测幽门螺杆菌DNA、cagA和EPIYA基序。EPIYA片段的类型和数量由电泳图谱确定。为确认PCR结果，对20个cagA 3'可变区扩增子进行测序，并进行计算机分析，使用MEGA 5软件预测氨基酸序列。计算比值比（OR）以确定EPIYA基序类型与胃部病变之间以及EPIYA-C片段数量与消化性溃疡和胃癌之间的关联。
结果
499例患者中有287例（57.5%）检测到幽门螺杆菌DNA，其中214例（74%）为cagA阳性。慢性胃炎患者中cagA阳性幽门螺杆菌的频率为74.6%（164/220），消化性溃疡患者中为73.6%（39/53），胃癌患者中为78.6%（11/14）。EPIYA-ABC模式在慢性胃炎患者中更常见（79.3%，130/164），而EPIYA-ABCC序列在消化性溃疡（64.1%，25/39）和胃癌患者（54.5%，6/11）中更常见。然而，携带EPIYA-ABCC cagA基因模式的个体患消化性溃疡（OR = 7.0，95%置信区间[CI] = 3.3 - 15.1；p < 0.001）和胃癌（OR = 5.9，95% CI = 1.5 - 22.1）的风险显著增加。
结论
cagA阳性幽门螺杆菌在墨西哥南部高度流行，所有CagA变体均为西方类型。编码EPIYA-ABCC基序模式的cagA等位基因与消化性溃疡和胃癌相关。
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