白细胞介素-1β和肿瘤坏死因子-α基因多态性对幽门螺杆菌相关胃癌前病变的协同作用。

Synergistic effect of IL-1β and TNF-α polymorphisms on the H. pylori-related gastric pre-malignant condition.

作者信息

Tahara Tomomitsu, Shibata Tomoyuki, Yamashita Hiromi, Yoshioka Daisuke, Okubo Masaaki, Yonemura Joh, Kamiya Yoshio, Ishizuka Takamitsu, Nakagawa Yoshihito, Nagasaka Mitsuo, Iwata Masami, Nakamura Masakatsu, Hirata Ichiro, Arisawa Tomiyasu

机构信息

Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.

出版信息

Hepatogastroenterology. 2012 Nov-Dec;59(120):2416-20. doi: 10.5754/hge10605.

DOI:10.5754/hge10605

PMID:23169178

Abstract

BACKGROUND/AIMS: We investigated the effect of IL-1β and TNF-α polymorphisms, and its synergistic effect with age, gender and H. pylori status on the gastric pre-malignant condition.

METHODOLOGY

IL-1β-31(T>C) and -511(C>T) and TNF-α-857 (C>T) polymorphisms were genotyped in 123 cancer free subjects. Degree of histological gastritis in both antrum and corpus, and extension of endoscopic gastric atrophy were also evaluated.

RESULTS

Significant associations were found between degrees of mononuclear cell infiltration (p=0.007) and atrophy (p=0.01) in the antrum with IL-1β-31(T>C) polymorphism, and degree of endoscopic gastric atrophy with both IL-1β-31(T>C), -511(C>T) polymorphisms (p=0.03, 0.04, respectively). When subjects were divided into the 3 groups according to the histological severity of gastric mucosal atrophy: the non-atrophic gastritis (NA) group (atrophy score=0 and metaplasia score=0), the severe atrophic gastritis (SA) group (atrophy score>=2 or metaplasia score>=2), and the mild atrophic gastritis (MA) group (all others), synergistic effect was found between numbers of IL-1β-31C, IL-1β-511T variant alleles with co-factors on the development of gastric atrophy in the antrum (gender + H. pylori + number of IL-1β-31C allele: p=0.001, age + gender + H. pylori + number of IL-1β-31C allele: p=0.0008, gender + H. pylori + number of IL-1β-511T allele: p=0.016, age + gender + H. pylori + number of IL-1β-511T allele: p=0.013), while such association was found for TNF-α-857 T allele in the antrum and all genotypes in the corpus.

CONCLUSIONS

IL-1β-31C, IL-1β-511T variant alleles may accelerate gastric mucosal inflammation and atrophy, not only by themselves, but also through the interaction with co-factors.

摘要

背景/目的：我们研究了白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）基因多态性，以及它们与年龄、性别和幽门螺杆菌感染状态对胃癌前病变的协同作用。

方法

对123名无癌受试者进行IL-1β -31（T>C）、-511（C>T）和TNF-α -857（C>T）基因分型。同时评估胃窦和胃体的组织学胃炎程度以及内镜下胃萎缩的范围。

结果

发现胃窦部的单核细胞浸润程度（p = 0.007）和萎缩程度（p = 0.01）与IL-1β -31（T>C）基因多态性显著相关，内镜下胃萎缩程度与IL-1β -31（T>C）、-511（C>T）基因多态性均显著相关（分别为p = 0.03、0.04）。根据胃黏膜萎缩的组织学严重程度将受试者分为3组：非萎缩性胃炎（NA）组（萎缩评分=0且化生评分=0）、重度萎缩性胃炎（SA）组（萎缩评分≥2或化生评分≥2）和轻度萎缩性胃炎（MA）组（其他所有情况），发现胃窦部IL-1β -31C、IL-1β -511T变异等位基因数量与协同因素在胃萎缩发展过程中存在协同作用（性别+幽门螺杆菌+IL-1β -31C等位基因数量：p = 0.001，年龄+性别+幽门螺杆菌+IL-1β -31C等位基因数量：p = 0.0008，性别+幽门螺杆菌+IL-1β -511T等位基因数量：p = 0.016，年龄+性别+幽门螺杆菌+IL-1β -511T等位基因数量：p = 0.013），而胃窦部TNF-α -857 T等位基因和胃体部所有基因型存在这种关联。