浙江汉族人群Toll样受体4基因多态性与幽门螺杆菌相关消化性溃疡的关系

背景：幽门螺杆菌（H.pylori）感染是消化性溃疡的主要病因,然而其致病性存在个体差异,可能与宿主遗传易感性和先天性免疫机制有关。Toll样受体（TLR）在机体的先天性抗感染免疫中起重要作用。目的：探讨浙江汉族人群TLR4基因Asp299Gly多态性与H.pylori相关消化性溃疡的关系。方法：以聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测118例浙江汉族消化性溃疡患者和210名健康对照者的TLR4基因Asp299Gly等位基因和基因型;行快速尿素酶试验和血清H.pyloriIgG检测判断H.pylori感染情况。结果：本组浙江汉族人群TLR4基因Asp299Gly均为AA纯合子基因型,未见突变基因型AG和GG。消化性溃疡组H.pylori感染率为94.9%,显著高于正常对照组的62.4%（P=0.000）;两组Asp299Gly基因型频率差异无统计学意义。结论：浙江汉族人群TLR4基因Asp299Gly多态性与H.pylori相关消化性溃疡无相关性。     

Toll样受体4基因多态性与消化性溃疡和幽门螺杆菌感染的相关性研究

背景：幽门螺杆菌（H．pylori）感染是消化性溃疡的主要病因。脂多糖（LPS）通过TOU样受体（TLR）4激活核因子（NF）-KB，在抗感染免疫应答中起启动和调节作用。TLR4基因发生Asp299Gly突变可中断TLR4介导LPS信号传导。目的：研究我国湖北省汉族人群TLR4基因Asp299Gly多态性与消化性溃疡和肌pylori感染的关系。方法：采用病例对照研究和聚合酶链反应-限制性片段长度多态性（PCR-RFLP）法．检测126例消化性溃疡患者和264名正常对照者的TLR4等位基因Asp299Gly基因型分布。结果：消化性溃疡者肌pylori阳性率（90．5％）显著高于正常对照组（61．7％）（P〈0．0001，OR=5．889，95％CI：3．089-11．216）。在H．pylori感染相关性消化性溃疡组和正常对照组中均未发现TLR4基因Asp299Gly的突变型，其基因型、等位基因以及携带者频率总体分布无显著性差异。结论：本研究未能显示TLR4基因Asp299Gly基因多态性与H.pylori感染、H．pylori相关性消化性溃疡形成有相关性。     

消化性溃疡发病相关因素演变的统计分析

近几十年来,消化性溃疡的流行病学特征在世界范围内发生了一些变化,但其在国人中的演变有待进一步了解.目的：研究消化性溃疡发病相关因素的演变情况.方法：对1987年1月～2003年12月在仁济医院接受胃镜检查而被诊断为消化性溃疡者的年龄、溃疡类型、幽门螺杆菌（H.pylori）感染等情况进行统计分析.将整个观察期分为1987～1990年、1991～1994年、1995～1999年和2000～2003年4个时间段作进一步分析.结果：在4个时间段中,十二指肠溃疡（DU）和胃溃疡（GU）的平均发病年龄均呈上升趋势（P＜0.01）,DU患者的平均年龄依次为42.5岁、43.6岁、44.6岁和47.4岁,GU依次为48.9岁、50.1岁、49.5岁和52.6岁.DU患者的平均年龄较GU年轻近6岁.DU与GU的总体发病人数之比介于1.84和2.99之间.男性的DU和GU检出率均高于女性,DU男女之比为1.45：1～2.59：1,GU为2.08：1～4.27：1.1997年,全体接受胃镜检查者、DU患者和GU患者的H.pylori阳性率分别为51.5%、78.5%和71.9%,至2003年则分别为31.0%、63.5%和58.0%.各组前后差异均有显著性（P＜0.01）.结论：近年来消化性溃疡,包括DU和GU的平均患病年龄有逐渐上升的趋势,患者仍以男性为主.胃镜检查者和消化性溃疡患者的H.pylori阳性率均有逐年下降的趋势.     

云南哈尼族彝族幽门螺杆菌感染人群胃癌易感基因研究

胃癌的发生是生物、环境、宿主等因素共同作用的结果．宿主遗传因素与幽门螺杆菌（H．pylori）感染后的不同临床结局有关。目的：筛选云南红河州哈尼族彝族Hpylori感染人群的胃癌易感基因,探讨不同基因型和等位基因与H．pylori感染宿主胃癌发病风险的相关性。方法：通过PubMed、CNKI和HapMap数据筛选出12个中国人群胃癌易感相关单核苷酸多态性（SNP）位点,以芯片技术对哈尼族彝族H．pylori感染慢性胃炎和胃癌患者的这些SNP位点进行分型。结果：IL-1β-3IC／T和IL-1β-511C/T位点存在完全连锁不平衡．其基因型（P=0．014）和等位基因频率（P=0．049）在胃癌和胃炎组中有显著差异,-511CT／-31CT（OR=2．256,95％CI：1．048～4．855）和-511TT/-31CC（OR=3．312,95％CI：1．462～7．502）基因型胃癌发病风险显著高于-511CC／-31TT基因型。COX-2．899C／G位点基因型频率在胃癌和胃炎组中有显著差异（P=0．033）,GG基因型胃癌发病风险显著高于CG基因型（OR=2．796,95％CI：1．053～7．423）。TNF—α-238A／G位点基因型频率在胃癌和胃炎组中有显著差异（P=0．037）．AA、AG基因型胃癌发病风险显著高于GG基因型（OR=2．600．95％CI：1．130～5．985）。结论：IL-1β-31C、IL-1β-511T等位基因和COX-2—899GG基因型可增高云南红河州哈尼族彝族Hpylori感染人群的胃癌发病风险,TNF-α-238GG基因型对上述人群的胃癌发生具有保护作用。     

胃癌易感性白细胞介素-1B基因突变检测芯片的初步临床应用

背景：白细胞介素（IL）-1B基因的单核苷酸多态性（SNP）与胃癌发生密切相关，幽门螺杆菌（H．pylori）感染增加了IL-1B基因突变型宿主胃癌发生的危险性。目的：检测IL-1B基因-31C/T和-511T／C两个位点的多态性．分析其准确性，指导胃癌易感人群的预测和H．pylori感染的个性化治疗，以防治胃癌。方法：取158例胃癌、24例十二指肠溃疡和50例慢性胃炎患者以及98名正常对照者的外周血基因组DNA为模板，聚合酶链反应（PCR）扩增样本IL-1B基因片段，应用Outdo胃癌易感性IL-1B基因突变检测芯片分析-31C／T和-511T／C的基因多态性．并通过测序验证芯片检测的正确性。结果：胃癌组IL-1B-31TT、-511CC和-31TT/511CC基因型的频率显著低于十二指肠溃疡组、慢性胃炎组和正常对照组（21．5％对58．3％、46．0％和57．1％；20．9％对58．3％、50．0％和52．0％；9．5％对45．8％、32．0％和32．7％）（P〈0．05），IL-1B-31CC、-511TT和-31CC／511TT基因型的频率则显著高于十二指肠溃疡组、慢性胃炎组和正常对照组（39．9％对16．7％、24．0％和7．1％；44.3％对12．5％、16．0％和8．2％：23.4％对4．2％、10．0％和5．1％）（P〈0．05）。与测序结果相比，20例基因芯片检测的准确率为100％。结论：IL-1B基因-31T-to-C、-511C-to-T突变与胃癌易感性增加有关。Outdo胃癌易感性IL-1B基因突变检测芯片的检测结果准确可靠．值得进一步研究以确定其临床应用价值。     

白细胞介素-1B-511单核苷酸多态性与胃癌关系的流行病学研究

目的研究中国胃癌高、低发区白细胞介素（IL）-1B-511单核苷酸多态性、幽门螺杆菌（Hp）感染与胃癌的芙系。方法胃癌高发区（陕西省）胃癌患者、健康志愿者各102例，胃癌低发区（广东省）胃癌患者、健康志愿者各104例，两组人群在性别比及年龄上均匹配。采用限制性片段长度多态性（PCR—RFLP）分析IL-1B-511单核苷酸多态性，酶联免疫吸附法（ELISA）检测血清抗Hp—IgG抗体。结果在胃癌低发区，胃癌患者IL-1B-511T／T基因型频率明显高于对照人群（26．9％比13．4％，X^2=5．85，P〈0．05；OR=2．37，95％CI为1．16～4．82）。在胃癌高发区，胃癌患者IL-1B-511 T／T基因型频率与对照人群尢明显差异（27．5％比24．5％，X^2=0．41，P〉0．05）；高发区对照人群的IL-1B-511 T／T基因型频牢明显高于低发区相应人群（24．5％比13．4％，X^2=4．1，P〈0．05）。Hp感染轻度增加低发区人群发生胃癌的危险性（OR=3．03，95％CI为1．61～5．71），而IL-1B-511 T／T基因型增加Hp感染后胃癌发生的危险性（OR=8．0，95％CI为1．39～35．7）。结论IL-1B-511 T／T基因型与中国人胃癌发生有关，IL-1B-511 T／T基因型增加HP感染后胃癌发生的危险性。     

宿主免疫基因多态性与幽门螺杆菌感染相关疾病的关系

幽门螺杆菌(Helicobacter pylori,H.pylori)感染与消化性溃疡、萎缩性胃炎、胃MALT(Mucosa-associated lymphoid tissue)淋巴瘤及胃癌等疾病的发生密切相关。H.pylori感染引起的不同临床结局主要与H.pylori致病因子、宿主因素和环境因素三方面有关。目前宿主基因易感性的差异在H.pylori感染致病的作用已成为研究热点,本文就宿主免疫基因的多态性与幽门螺杆菌感染所致疾病关系的研究进行总结,从宿主TOLL样受体、NOD受体、CD14及HLA等免疫因子基因多态性进行综述。     

福建省胃癌和十二指肠溃疡患者白细胞介素1基因多态性的比较

目的了解福建省胃癌和十二指肠溃疡患者中白细胞介素1（IL-1）基因多态性的分布并进行比较。方法病理确诊的144例胃癌及排除非甾体类抗炎药服用史的102例十二指肠溃疡患者，采用PCR—RFLP分析检测IL-1基因多态性。结果（1）胃癌患者中，IL-1B-511基因型CC、CT、rlT分别占18．1％、48．6％和33，3％，IL-1RN等位基因检测到A1、A2、A4三种，基因型A1／A1、A1／A4、A1／A2、A2／A2分别占88．9％、1．4％、9．0％、0，7％；十二指肠溃疡患者中，IL-1B-511基因型CC、CT、TT分别占19．6％、59，8％和20．6％，IL-1RN等位基因检测到A1、A2两种，基因型A1／A1、A1／A2分别占90，2％、9，8％。（2）IL．1B-511 TT基因型在胃癌患者中的比例与在十二指肠溃疡患者中的比例差异显著（x^2=4.806，P=0．028）；不同IL-1 RN基因型在胃癌的比例与在十二指肠溃疡中的比例无统计学差异。结论福建省胃癌和十二指肠溃疡患者IL-1基因型均以IL-1B-511基因CT型、IL-1RN基因型以A1／A1为主。IL-1 B-511 TT基因型可能与福建省胃癌的高发有关。     

IL-1B基因多态性与幽门螺旋杆菌感染后胃癌发病的关系

取35例胃癌(胃癌组)及37例慢性胃炎(对照组)患者全血标本,使用基因芯片检测技术,结合PCR 体外扩增方法,检测人IL1B-31和-511位点基因多态性,并用13C尿素呼气试验、免疫印迹试验检测Hp感染情况.结果胃癌组Hp感染率高于对照组(P＜0.05),胃癌组IL-1B-31位点T携带子的频率高于对照组(P＜0.05).与C/C型比较,T携带子基因型者发生胃癌的风险增加,OR=4.237(95%CI:1.563～10.000);IL-1B-511位点的各基因型频率在两组间差异无统计学意义(P＞0.05).认为IL-1B-31位点基因多态性可能增加Hp感染后中国人发生胃癌的危险性.     

消化性溃疡患者血管活性肠肽与十二指肠胃反流和幽门螺杆菌感染关系的研究

背景：消化性溃疡（PU）和十二指肠胃反流（DGR）患者的血浆血管活性肠肽（VIP）含量常高于正常水平，而幽门螺杆菌（H.pylori)感染可能参与PU的发病。目的：探讨PU患者的VIP和DGR和H.pylori感染的关系。方法：采用放射免疫测定（RIA）检测34例胃溃疡（GU）患者、42例十二指肠球部溃疡（DU）患者和30例健康人的血浆VIP含量；放射性核素^99mTc-EHIDA显像法测定DGR；双抗体夹心酶联免疫吸附测定（ELISA）检测血清H.pylori IgG抗体，Giemsa染色检测胃黏膜H.pylori。结果：GU组的血浆VIP含量显著高于DU组和正常对照组（P＜0．01）；DGR阳性率亦显著高于DU组（P＜0．05）。DGR阳性组的血浆VIP含量显著高于DGR阴性组（P＜0．01）。H.pyori阳性组的血浆VIP含量显著低于H.pylori阴性组（P＜0．05）。结论：PU患者血浆VIP含量升高可能是DGR发生的重要因素之一。     

Association between interleukin-1 gene polymorphisms and Helicobacter pylori infection in gastric carcinogenesis in a Chinese population

BACKGROUND AND AIM: Helicobacter pylori is a major cause of chronic gastritis and peptic ulcer disease and a definite carcinogen for gastric adenocarcinoma. However, the underlying pathogenic mechanisms are not fully understood. Interleukin-1 (IL-1) is a key cytokine involved in H. pylori-induced gastric inflammation. The present study aimed to determine polymorphisms of IL-1B and IL-1 receptor antagonist (IL-1RN) genes and their association with H. pylori infection and gastroduodenal diseases in Chinese patients. METHODS: Three hundred and ninety-nine patients with gastroduodenal diseases (129 chronic gastritis, 127 duodenal ulcer and 143 non-cardiac gastric cancer) and 264 healthy controls were genotyped for IL-1B-511 and IL-1RN gene polymorphisms by the PCR-RFLP method. H. pylori infection status was determined by a validated serological test. RESULTS: The frequency of IL-1B-511 T allele was significantly higher in H. pylori positive patients with non-cardiac gastric cancer than in both H. pylori negative patients with non-cardiac gastric cancer (60%vs 46%, P = 0.0342, OR = 1.666, 95% confidence interval [CI]: 1.045-2.656) and in healthy controls (60%vs 48%, P = 0.0071, OR = 1.665, 95%CI: 1.149-2.412). However, the polymorphism was not associated with chronic gastritis and duodenal ulcer. Multivariate logistic regression analyses identified that IL-1B-511 T/T carrier status was an independent risk factor for non-cardiac gastric cancer in the presence of H. pylori infection (adjusted OR = 3.01, 95%CI: 1.27-7.11, P = 0.01), and the frequency of IL-1B-511 T allele was an increased risk factor for developing gastric cancer (P = 0.03, adjusted OR = 2.29, 95%CI: 1.08-4.86). There was no association between IL-1RN gene polymorphisms and H. pylori infection and other gastroduodenal diseases. CONCLUSION: IL-1B-511 T allele is associated with H. pylori infection in non-cardiac gastric cancer in a Chinese population. The IL-1B-511 gene polymorphism appears to play an important role in gastric carcinogenesis in Chinese patients with H. pylori infection.     

Interleukin 1beta polymorphisms increase risk of hypochlorhydria and atrophic gastritis and reduce risk of duodenal ulcer recurrence in Japan

BACKGROUND & AIMS: Interleukin-1 beta (IL-1beta) polymorphisms are associated with increased risk of gastric cancer in whites. This study aimed to examine effects of these polymorphisms on gastric acid secretion, atrophic gastritis, and risk of peptic ulcer in Japan. METHODS: We determined IL-1B-511/-31 and IL-1RN genotypes and measured gastric juice pH, serum pepsinogen (PG) I and II levels, and gastritis and atrophy scores in Helicobacter pylori-positive patients with gastritis only, gastric ulcers, or duodenal ulcers (DUs), and H. pylori-negative controls. RESULTS: In the H. pylori-positive group, subjects with the proinflammatory IL-1B-511 T/T genotype had the highest atrophy and gastritis scores, the highest median gastric juice pH, and the lowest median serum PG I/PG II ratios. Although gastric juice pH significantly increased and serum PG I and PG I/PG II ratios significantly decreased in the IL-1B-511 T/T genotype group with age, no such age-dependent changes were observed in the C/C genotype group. Changes in the C/T genotype group were intermediate. In the H. pylori-negative group, the IL-1 loci had no effect on any of the physiologic or morphologic parameters. Carriage of IL-1RN allele 2 significantly protected against DU disease while the IL-1B-511 T/T genotype significantly protected against DU recurrence in patients older than 60 years. CONCLUSIONS: Proinflammatory IL-1beta polymorphisms are associated with hypochlorhydria and atrophic gastritis in Japan. The effects are dependent on H. pylori infection and become more significant with advancing age. This may explain the high incidence of gastric cancer in Japan and also the age-dependent decrease in DU recurrence in infected subjects.     

IL1B and IL1RN polymorphic genes and Helicobacter pylori cagA strains decrease the risk of reflux esophagitis

BACKGROUND & AIMS: Proinflammatory interleukin (IL)-1 gene polymorphisms associated with high levels of IL-1beta activity increase the risk for hypochlorhydria and distal gastric carcinoma. The aim of this study was to evaluate whether carriers of these polymorphic genes are protected against gastroesophageal reflux disease (GERD). TNFA-308 polymorphisms were also studied. METHODS: We prospectively evaluated 385 patients without gastric cancer and peptic ulcer. Of these patients, 383 (98 with GERD and 285 controls) were successfully genotyped for all cytokines studied. The cagA status of Helicobacter pylori isolates was determined by polymerase chain reaction (PCR). IL1B-511/-31, IL1RN, and TNFA-308 polymorphisms were genotyped by PCR, PCR/restriction fragment length polymorphism, or PCR/confronting 2-pair primers. Histologic gastritis was assessed according to the updated Sydney system. The role of the proinflammatory cytokine genotypes in the genesis of GERD was evaluated before and after stratification by H. pylori status in logistic regression models controlling for confounding factors. RESULTS: IL1B-31 (a near-complete linkage disequilibrium between polymorphism at -31 and -511 was found) and IL1RN*2 allele polymorphisms were associated with GERD. After stratification, in the group of H. pylori-positive patients, cagA-positive status, IL1B-31 polymorphic alleles, IL1RN*2 alleles, and the degree of corpus gastritis were negatively associated with GERD. In the H. pylori-negative group, IL1B-31C/C genotype was inversely associated with GERD even after adjustment for age and sex. CONCLUSIONS: This study provides evidence supporting the independent protective role of cagA-positive H. pylori status and IL1B and ILRN allele polymorphisms against GERD.     

Role of host interleukin 1β gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) polymorphisms in clinical outcomes in Helicobacter pylori-positive Turkish patients with dyspepsia

BACKGROUND: Helicobacter pylori infection leads to different clinical outcomes depending on both host and bacterial factors. In a recent study, we identified H. pylori cagE and babA2 genotypes as independent predictors of duodenal ulcer (DU) and gastric cancer (GC) in dyspepsia patients, but no previous studies have examined the role of host-related genetic factors in Turkey. This time our aim was to evaluate whether polymorphisms of the interleukin 1B (IL-1B) and the interleukin 1 receptor antagonist (IL-1RN) genes are important factors in the differential expression of gastroduodenal diseases in H. pylori-positive dyspepsia patients. METHODS: Ninety-three H. pylori-positive patients, 30 with nonulcer dyspepsia (NUD), 30 with DU, and 33 with GC, were investigated. The IL-1B-511 and IL-1B-31 biallelic polymorphisms, and the IL-1RN intron 2 variable number tandem repeat were genotyped by polymerase chain reaction and single-strand confirmation polymorphism analysis. RESULTS: The IL-1RN-1/1 genotype was significantly more prevalent among patients with NUD than among those with GC (chi(2) = 9.270; P = 0.002), and the IL-1RN-1/2 genotype was significantly more common in patients with GC (chi(2) = 6.01; P = 0.014). Multivariate regression analysis showed that cagE, babA2, and IL-1RN-1/2 genotypes were independent predictors of GC, but when patients with benign disorders were grouped together (NUD + DU) and compared with patients with GC, regression analysis disclosed that babA2 (P = 0.000) and IL-1B-31 gene polymorphisms (CC or CT) (P = 0.01) were the only independent markers of GC. CONCLUSIONS: When analyzed together with host genetic factors, the wellestablished bacterial risk factor babA2 seems to be the most important predictor of malignant disorders, and the presence of the IL-1B-31TT genotype emerges as a protective factor against them.     

Association of polymorphisms of interleukin-1 beta gene and Helicobacter pylori infection with the risk of gastric ulcer

BACKGROUND/AIMS: Interleukin-1 beta (IL-1 beta) plays an important role in gastric inflammation and physiology. Functional polymorphisms of IL-1 beta gene have been related to different risks of gastric cancer and duodenal ulcer but their role in gastric ulcer remains unknown. In this study, we investigate a plausible association between gastric ulcer and the polymorphisms in the IL-1 beta and IL-1 receptor antagonist (IL-1RN) genes. The relationships among the cytokine genotyping, other environmental risks such as Helicobacter pylori infection and smoking, and clinical characteristics of gastric ulcer were also determined. METHODOLOGY: Peripheral blood DNAs from 120 unrelated Taiwan Chinese patients with gastric ulcer and 238 ethnically matched healthy controls were genotyped for the promoter (position -31 and -511) and Taq I polymorphism (position +3954) in the IL-1 beta gene and the variable number of tandem repeats polymorphisms in intron 2 of the IL-1RN gene. The status of Helicobacter pylori infection was determined by serology. RESULTS: The seropositive rate of Helicobacter pylori (95/120 vs. 134/238, OR: 2.95, 95%CI 1.77-4.91), habitual smoking (67/120 vs. 82/238, OR: 2.40, 95%CI 1.54-3.77) and blood group O (63/120 vs. 98/238, OR: 1.55, 95%CI 1.0-2.41) were significantly higher in patients with gastric ulcer than controls. The distributions of allele frequencies of IL-1 beta (-31 C/T or -511 C/T or +3954) and IL-1RN were similar between patients with gastric ulcer and controls. No significant differences were observed, including those analyzed after stratification of the infected population and by the ulcer subgroup. CONCLUSIONS: Our data suggested that Helicobacter pylori infection, cigarette smoking, and blood group O are risk factors of gastric ulcer and IL-1 beta or IL-1RN polymorphisms do not influence susceptibility to gastric ulcer in a Taiwanese population.     

The role of interleukin-1beta gene polymorphism in the gastric carcinogenesis]

BACKGROUND/AIMS: This study was aimed to investigate the polymorphism of interleukin-1beta(IL-1B) and IL-1 receptor antagonist (IL-1RN) gene and the relationship between genotypes and development of gastric adenocarcinoma in Korean, and to investigate the role of Helicobacter pylori (H. pylori) infection. METHODS: The study population comprised of 258 patients with gastric adenocarcinoma. They were classified according to Lauren's classification and the status of H. pylori infection. Genomic DNA was extracted from the gastric tissue. As a control, genomic DNA from peripheral lymphocyte of 100 healthy individuals was used. The amplified products of -511 bp and -31 bp fragments in the IL-1B by PCR were digested by restriction enzyme and separated for RFLP. Variable number tandem repeats were amplified and subjected to RFLP of IL-1RN. RESULTS: There was no significant difference in the genotype of IL-1B-511T and IL-1B-31C between the adenocarcinoma group and the control group. IL-1RN allele 1 homozygote in the intestinal type showed high frequency of 91.7% (p=0.007). In the H. pylori-positive group of the adenocarcinoma, the frequency of IL-1B-31C was significantly higher than that of H. pylori-negative group (p=0.045). CONCLUSIONS: The single nucleotide polymorphism of IL-1B-31C may contribute to the development of the gastric adenocarcinoma in the H. pylori-positive population.     

Influence of inflammatory cytokine polymorphisms on eradication rates of Helicobacter pylori

Pro-inflammatory cytokines and anti-inflammatory cytokines are produced in gastric mucosa from inflammatory cells activated by Helicobacter pylori (H. pylori) infection. Of the inflammatory cytokines, interleukin (IL)-1β and tumor necrosis factor (TNF)-α have a potent inhibitive effect on gastric acid production. Polymorphisms in these genes are associated with individual differences in cytokine messenger RNA levels, which result in different gastric mucosal inflammation, different acid inhibition and different gastroduodenal disease risks in response to H. pylori infection. The sustained higher intragastric pH during an eradication therapy is known to be one of the therapeutic determinants of the H. pylori eradication as well as antibiotics resistance and poor compliance. The IL-1B- 511 polymorphism is related to eradication rate, and, in combined analysis of previous reports, the eradication rate in patients with the IL-1B- 511 C/C genotype (77.4%, 209/270), low IL-1β producer genotype, is lower than that of the IL-1B- 511 C/T and T/T genotypes (87.2%, 631/724) (Odds ratio for eradication failure: 1.98, 95% confidence interval: 1.38–2.84, P  = 0.0002). Moreover, the odds ratio of combined CYP2C19 rapid metabolizer- IL-1B- 511 C/C type for eradication failure is 11.15 (5.23–23.78) times that of the CYP2C19 poor metabolizer- IL-1B- 511 non-C/C type. However, there is no positive data indicating the role of other inflammatory cytokine polymorphisms (e.g. IL-1RN , TNF-A or IL-10 ) in eradication therapy. Nevertheless, the studies show that inflammatory cytokine polymorphisms, especially the IL-1B- 511 T/T genotype, are the determinants of eradication by affecting gastric acid secretion and mucosal inflammation. Therefore, the tailored eradication therapy, considering inflammatory cytokine polymorphisms, may be effective for the higher eradication rates.     

Association of H pylori cagA and vacA genotypes and IL-8 gene polymorphisms with clinical outcome of infection in Iranian patients with gastrointestinal diseases

AIM: To find out if a functional promoter polymorphism in the IL-8 gene along with cagA status and polymorphisms in vacA gene influence the type of diseases in Iranian patients infected by H pylori. METHODS: IL-8 -251 A/T polymorphism was genotyped by oligonucleotide allele specific PCR (ASO-PCR) in a sample of 233 patients with H pylori infection undergoing upper gastrointestinal endoscopy. The presence of cagA gene and polymorphisms in vacA gene was also determined by PCR. Association of these genetic polymorphisms with the development of gastritis, peptic ulcers as well as gastric cancer was tested. RESULTS: When the patients with different clinical manifestations were compared according to the presence of cagA gene or various vacA genotypes, only the vacA genotypes were significantly different among gastritis, peptic ulcer and gastric cancer patients (x2= 17.8; P=0.001). Furthermore, there was a significant difference in the frequency of IL-8 -251 A/T genotypes between patients with gastric cancer and benign diseases (x2= 10.47; P = 0.005). CONCLUSION: The IL-8 -251 A/T polymorphism and the polymorphisms in H pylori vacA gene are involved in limiting the infection outcome to gastritis and peptic ulcer or in favoring cancer onset in Iranian patients.     

Recurrence of Helicobacter pylori infection and the long-term outcome of peptic ulcer after successful eradication in Japan.

Recurrence of peptic ulcer after successful eradication of Helicobacter pylori is closely associated with reinfection. The aim of this study was to examine the recurrence of peptic ulcer and reinfection with H. pylori after successful eradication. To eradicate H. pylori infection, patients with active peptic ulcer disease were assigned to two treatment groups depending on the year of their enrollment (AM group and OAMR group). Patients in the AM group received 400 mg of cimetidine twice per day, 300 mg of amoxicillin three times per day, and 250 mg of metronidazole three times per day for 2 weeks. Patients in the OAMR group received 20 mg of omeprazole once per day, 500 mg of amoxicillin granules three times per day, 250 mg of metronidazole three times per day, and 150 mg of roxithromycin twice per day for 1 week. After endoscopy verified ulcer scarring and successful eradication of H. pylori infection, study patients were followed up monthly and did not undergo acid-suppressive therapy. Endoscopy was performed at 6-month intervals for the 1st year. After the 1st year, follow-up endoscopies were performed annually. In total, 107 patients with peptic ulcer (duodenal ulcer [DU], 65; gastric ulcer [GU], 42) were followed up for a mean period of approximately 2 years. Recurrence of infection occurred in 10 (9.3%) of 107 patients (AM group, 9; OAMR group, 1) after 210 patient-years of follow-up; the recurrence rate was 4.8% per patient-year. Recurrence of H. pylori infection was significantly higher in the AM group (23.1%) than in the OAMR group (1.5%). H. pylori infection recurred in two patients 6 months after eradication therapy, in seven 1 year after, and in one 2 years after. Thereafter, no further cases of H. pylori recurrence were observed. During follow-up periods, seven cases of ulcer recurrence were observed (DU, 4; GU, 3). The rate of peptic ulcer recurrence within 2 years after eradication therapy was significantly higher than that after more than 2 years. Four cases of ulcer recurrence (DU, 3; GU, 1) also had recurrence of H. pylori infection. One recurrent case of DU without reinfection was associated with nonsteroidal anti-inflammatory drugs. The remaining two cases of GU recurred without H. pylori reinfection. In conclusion, peptic ulcer recurrence rarely occurred (3 [2.9%] of 103) in patients cured of H. pylori infection. Reinfection after apparent successful eradication was rarely noted when a powerful therapeutic regimen in eradication was used. Therefore, to eradicate H. pylori, a highly effective therapeutic regimen should always be used.     

Clinical relevance of Helicobacter pylori CagA-positive strains: gastroduodenal peptic lesions marker.

OBJECTIVES: peptic ulcer is characterized by its recurrent nature, which necessitates maintenance treatment in most patients. But this natural history can be changed in patients with peptic ulcer associated to Helicobacter pylori, as shown by the low rates of recurrence and decreased hemorrhagic recidivism associated with this infection. Whether CagA or VacA strains are associated with a greater risk of peptic ulcer is controversial. This study was designed to examine endoscopic findings and their relation with H. pylori phenotype (CagA or VacA). METHODS: 106 selected dyspeptic patients underwent upper gastrointestinal tract endoscopic examination between September 1996 and May 1997 [69 with H. pylori (Hp) and 37 without this infection]. Endoscopic findings were classified as gastric ulcer (GU), duodenal ulcer (DU), gastric erosions (GE), duodenitis (Du), chronic gastritis (CG) and normal mucosa (NM). Hp phenotype was analyzed with a western blot test. RESULTS: 75% of H. pylori strains were CagA-positive and 54.2% were VacA-positive. 82.4% of the cases of DU were associated with a CagA+ phenotype, but the association was not statistically significant. Otherwise 100% of gastric ulcers were associated with CagA+ strains (p < 0.005). VacA phenotype was not associated with any particular endoscopic finding. Peptic ulcer (DU or GU) was also associated with the CagA+ phenotype (p < 0.05). CONCLUSIONS: the CagA+ H. pylori phenotype seems to be a peptic lesion marker, but was more frequently related with GU than with DU in our sample of Spanish patients.