The polymorphism interleukin 8-2251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population
The polymorphism interleukin 8-2251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population
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DOI：
10.1136/gut.2003.033050
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发表时间：
2005-03-01
期刊：
影响因子：
24.5
通讯作者：
Shimosegawa, T
中科院分区：
文献类型：
--
作者：
Ohyauchi, M;Imatani, A;Shimosegawa, T
背景资料：幽门螺杆菌感染与多种临床结局相关，包括胃十二指肠疾病，遗传因素可能与此过程相关。目的：我们研究白细胞介素8（IL-8）基因多态性对胃十二指肠疾病风险、幽门螺杆菌诱导胃炎程度和IL-8基因转录的影响。该研究在244名健康对照受试者和690名幽门螺杆菌阳性的非贲门胃癌、胃溃疡、十二指肠溃疡或胃炎患者中进行。采用直接序列分析法检测IL-8基因2251 A/T多态性，并测定胃炎评分和血清胃蛋白酶原（PG）水平。结果：IL-8基因2251 A与胃癌和胃溃疡的发病风险相关。携带IL-8 2251 A的患者显示胃癌（比值比（OR）2.01（95%置信区间（CI）1.38 - 2.92））和胃溃疡（OR 2.07（95% CI 1.37 - 3.12））的风险增加。与年龄小于49岁的患者相比，2251 A携带者胃窦萎缩和化生评分显著高于T/T携带者，PG I/II比值显著低于T/T携带者。在体外试验中，IL-8 2251 A表现出增强的启动子活性响应IL-1 β或肿瘤坏死因子α。结论：IL-8 2251 A等位基因可能与幽门螺杆菌感染患者胃萎缩的进展，并可能增加胃癌和胃溃疡的风险在日本人。
Background: Helicobacter pylori infection is associated with variable clinical outcomes, including gastroduodenal diseases, and genetic factors may be relevant in this process.Aims: We investigated the effects of an interleukin 8 (IL-8) gene polymorphism on the risk of gastroduodenal diseases, the degree of H pylori induced gastritis, and IL-8 gene transcription.Subjects: The study was performed in 244 healthy control subjects and 690 H pylori positive patients with non-cardia gastric cancer, gastric ulcer, duodenal ulcer, or gastritis.Methods: We identified the IL-8 2251 A/T polymorphism by direct sequence analysis, and measured the gastritis score and serum pepsinogen ( PG). The transcriptional promoter activity of the IL-8 gene was assessed by luciferase assay.Results: IL-8 2251A was associated with a higher risk of gastric cancer and gastric ulcer. Patients carrying IL-8 2251A showed an increased risk of gastric cancer ( odds ratios ( OR) 2.01 (95% confidence interval (CI) 1.38 - 2.92)) and gastric ulcer ( OR 2.07 ( 95% CI 1.37 - 3.12)). Compared with patients younger than 49 years, atrophy and metaplasia scores in the antrum were significantly higher and the PG I/II ratio significantly lower in 2251A carriers than in T/T carriers. In the in vitro assay, IL-8 2251A showed enhanced promoter activity in response to IL-1beta or tumour necrosis factor alpha.Conclusions: The IL-8 2251A allele may be associated with progression of gastric atrophy in patients with H pylori infection, and may increase the risk of gastric cancer and gastric ulcer in Japanese people.