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。     

人群TLR基因多态性与间日疟原虫感染的相关性

目的　比较间日疟原虫感染人群的Toll样受体（Toll-like receptor, TLR）5、TLR9基因3个单核苷酸多态性（single nucleotide polymorphism, SNP）位点差异,探讨其与间日疟原虫不同感染类型的相关性。方法　收集中缅边境地区（云南省盈江县和缅甸拉咱市）2017—2019年间日疟原虫感染者202例及健康对照者104例,将上述研究对象分为无症状感染组、有症状感染组及健康对照组,其中无症状感染组与有症状感染组统称为感染组;采用飞行时间质谱分型技术检测以上研究对象TLR5、TLR9基因3个SNP位点,分析不同组之间TLR5、TLR9基因SNP位点等位基因和基因型的分布差异。结果　3组研究对象之间性别与年龄分布差异均无统计学意义（P均＞0.05）;3组之间TLR9 1486C/T位点、TLR9 G1174A位点和TLR5 R392Stop位点的等位基因分布差异均无统计学意义（P均＞0.05）;健康对照组与感染组间及健康对照组与无症状感染组间TLR9 1486C/T位点的AG基因型分布差异均有显著性统计学意义（P均＜0.05）;3组之间TLR9 G1174A位点、TLR5 R392Stop位点的基因型分布差异均无统计学意义（P均＞0.05）。结论　TLR9 1486C/T位点的基因型多态性与间日疟原虫感染相关,但尚未发现TLR9 G1174A位点、TLR5 R392Stop位点与间日疟原虫感染的相关性,本研究结果可为揭示宿主基因多态性对间日疟原虫感染的影响提供重要线索。     

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。     

TLR4基因Asp299Gly及TLR2基因Arg753Glu、Arg677Trp多态性与中国湖北汉族炎症性肠病无相关性

目的:研究TLR4基因Asp299Gly及LTLR2基因 Arg753Glu及Arg677Trp多态性在中国汉族人群中的分布,探讨其与炎症性肠病的相关性．方法:采用聚合酶链反应-限制性片段长度多态性方法,检测120例中国湖北汉族炎症性肠病患者与110例正常对照者TLR4 基因ASp299Gly及TLR2基因Arg753Glu及 Arg677Trp基因型,分析该基因多态性与炎症性肠病以及临床亚型的相关性．结果:炎症性肠病患者和健康对照者均未检测出TLR4基因ASp299Gly及TLR2基因 Arg753Glu及Arg677Trp突变型．结论:TLR4基因Asp299Gly及TLR2基因 Arg753Glu及Arg677Trp基因多态性与中国湖北汉族人群炎症性肠病的易感性无相关性．     

幽门螺杆菌感染与Toll样受体

Toll样受体(TLR)是固有免疫系统中的细胞跨膜受体及微生物相关分子模式识别受体之一,可激活固有免疫应答,同时还是连接固有免疫和获得性免疫的桥梁。因此,Toll样受体在免疫系统中有着十分重要的作用。最近研究发现TLR信号通路和幽门螺杆菌(Hp)的感染和致病关系密切。此文主要介绍TLR的结构、信号通路及其在Hp感染和致病中的作用。     

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。     

幽门螺杆菌感染宿主炎性因子基因多态性与胃癌的关系

幽门螺杆菌(Hp)感染被认为是胃癌发生发展的重要危险因素,而基因多态性可能是Hp感染导致不同结局的内在因素,此文综述了与Hp感染诱导的胃癌发病有关的宿主炎性因子的基因多态性。     

RUNX3基因多态性、幽门螺杆菌感染与甘肃武威地区胃癌高发的相关性

目的探讨人Runt相关转录因子(RUNX)3基因多态性、幽门螺杆菌(Hp)感染与甘肃武威地区人群胃癌高发的相关性。方法选取武威地区118例胃癌患者为病例组,同期健康人群112例为对照组,使用酶联免疫吸附试验检测人群Hp感染状况,通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测RUNX3基因多态性。结果 RUNX3基因rs760805位点多态性与武威地区胃癌高发有相关性,等位基因A携带者(包括TA和AA两种基因型)与TT基因型相比胃癌发病风险增加1.764倍(OR=1.764,95%CI:1.005~3.097,P=0.041);RUNX3基因rs11249206位点多态性与武威地区胃癌高发没有相关性。病例组和对照组Hp感染阳性率分别为68.6%和51.8%,二者差异显著(P=0.009),Hp感染与RUNX3基因rs760805位点多态性存在交互作用,胃癌发病风险增加2.377倍(OR=2.377,95%CI:1.092~5.171,P=0.027)。结论 RUNX3基因rs760805位点多态性与武威地区胃癌高发相关,与Hp感染存在交互作用。     

CD14及Toll样受体4基因多态性与大肠癌的相关性研究

目的探讨我国湖北汉族人Toll样受体（TLR）4基因Asp299Gly和CD14 C-260T基因多态性分布与大肠癌的相关性。方法采用聚合酶链反应限制性片段长度多态性（PCR—RFLP）方法，检测110例大肠癌患者及160例正常对照者TLR4基因Asp299Gly及CD14 C-260T基因型及等位基因频率的分布。结果大肠癌组CD14 C-260T基因型与正常对照组比较，差异有统计学意义（P〈0．05）。正常对照组CC基因型的频率为15．6%，明显低于大肠癌组的31．8％（P=0．0027，OR=0．3968，95％CI=0．2209～0．7129）；正常对照组中CT基因型的频率为48．1％，明显高于大肠癌组的30．9％（P=0．0056，OR=2．074，95%CI=1．246～3．452）。所有样本中均未发现TLR4基因Asp299Gly的突变型。结论CD14 C-260T基因多态性与中国湖北汉族大肠癌显著相关，而TLR4基因Asp299Gly多态性与大肠癌无关。     

幽门螺杆菌与TLR4关系的研究进展

幽门螺杆菌（Hp）是人类慢性胃炎、消化性溃疡、胃癌等疾病的主要致病因子。其致病机制的影响因素除感染细菌数量、毒力和环境因素外,还包括宿主免疫机制、遗传易感性、胃肠黏膜内环境等。人类Toll样受体（TLPa）是表达于细胞膜上,与免疫系统识别微生物有关的一类受体家族,是能识别特定类型微生物的保守分子成分,即PAMP,可介导天然免疫和获得性免疫。     

Toll样受体4在幽门螺旋杆菌感染致动脉粥样硬化中的作用

动脉粥样硬化(As)是一种慢性炎症反应性疾病,幽门螺旋杆菌(Hp)感染与As性疾病的相关性研究日益引起关注,其促进As进展的具体机制尚未完全阐明。Toll样受体4(TLR4)是天然免疫反应的重要受体,在微生物致病因子及其产物引起宿主主动和被动免疫中有重要作用,参与动脉硬化的发生和发展。TLR4在As形成的多种细胞均有表达。TLR4通过捕获Hp的致病因子脂多糖后启动细胞内信号途径,进而引起核因子κB依赖的转录,引起一系列细胞因子及化学因子的释放,增强炎症反应而致病。本文就Hp、TLR4信号通路及其在As中的作用作一综述,为As疾病的防治提供新思路。     

新疆维吾尔族慢性胃炎患者HLA-DRB1等位基因与幽门螺杆菌感染的关系

目的研究新疆维吾尔族慢性胃炎患者HLA-DRB1等位基因与幽门螺杆菌（Hp）感染的关系。方法采用幽门螺杆菌分离培养技术检测33例维吾尔族慢性胃炎患者幽门螺杆菌感染情况,采用PCR-SSP检测HLA-DRB1＊0405、HLA-DRB1＊08、HLA-DRB1＊12等位基因,并与36例汉族慢性胃炎患者进行比较。结果1）新疆维吾尔族慢性胃炎患者Hp阳性率（78.8%）显著高于汉族慢性胃炎患者（58.3%）（P〈0.05）;2）维吾尔族、汉族慢性胃炎患者Hp感染与HLA-DRB1＊0405、HLA-DRB1＊08、HLA-DRB1＊12等位基因无相关性（P〉0.05）。结论1）维吾尔族慢性胃炎患者Hp感染率高于汉族慢性胃炎患者;2）维吾尔族、汉族慢性胃炎患者Hp感染与HLA-DRB1＊0405、HLA-DRB1＊08、HLA-DRB1＊12等位基因无关。     

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.     

No Evidence of an Association between Helicobacter pylori Infection and Raynaud Phenomenon

Background: Raynaud phenomenon (RP) is a vasospastic condition that manifests itself as cold-induced ischemic attacks of the fingers with skin color changes. It may be classified as primary (PRP) or secondary (SRP), if associated to other diseases, mainly connective-tissue diseases. Recently, the association between PRP and Helicobacter pylori infection has been reported. The aims of this study were to evaluate the prevalence of gastric H. pylori infection in a large group of patients affected by PRP and SRP and to assess whether it was more evident in patients with more recent onset of RP. Methods: Ninety-eight consecutive patients (93 F and 5 M), referring to our videocapillaroscopic service for the diagnosis of vascular and connective-tissue diseases, were evaluated. Forty-nine of them were affected by PRP and 49 by SRP. Patients were classified as having PRP on the basis of normal serological and immunological findings, normal videocapillaroscopic examination and exclusion of other conditions inducing RP. H. pylori infection was diagnosed by ¹³C-urea breath test (UBT). Two groups of 49 age-and sex-matched controls, respectively, were also evaluated. Results: Patients with SRP resulted significantly older than those with PRP (P < 0.006). UBT was found positive in 22/49 patients with PRP (45%) and in 29/49 patients with SRP (59%). The positivity of the respective control groups was 36% and 53% (P = NS). There was no higher prevalence of H. pylori infection in patients with RP lasting for less than 4 years. Conclusions: The results do not confirm the previously reported high prevalence of H. pylori infection in patients with PRP. A high association was not even found between the presence of the microorganism and SRP. There was no difference in the prevalence of H. pylori infection among the subgroups with more recent onset of both PRP and SRP.     

大蒜在治疗幽门螺杆菌感染中的作用

目的研究大蒜对幽门螺杆菌（Helicxobacter pylori，Hp）的根除作用。方法将Hp感染者随机分成三组，分别给予三联疗法、大蒜、三联疗法＋大蒜联合治疗，观察其Hp根除率。结果三联疗法、大蒜、三联疗法＋大蒜联合治疗对Hp根除率分别是81.82％、78．18％、92．73％。对比结果显示：三联疗法、大蒜对Hp根除率无显著差异（P〉0．05），而三联疗法＋大蒜联合治疗对Hp根除率与三联疗法和大蒜组有显著差异（P〈0．05）。对三联疗法耐药的Hp感染者继续应用大蒜治疗，又有5例病人Hp被根除。结论大蒜对Hp的根除作用与三联疗法等效，与三联疗法联合应用有协同作用，对已耐药的Hp仍有抑制作用。     

Non-urease producing Helicobacter pylori in chronic gastritis

Background: Helicobacter pylori infection is the commonest cause of gastritis. Different patterns of immune response to H. pylori infection and characteristics of bacteria are considered to contribute to clinical outcomes. Aim: To determine characteristics of the host H. pylori relationship in subjects with non‐ulcer dyspepsia and a histological diagnosis of gastritis. Methods: Thirty‐five subjects with chronic gastritis undergoing endoscopy (mean age 53 years, range 24–82, 14 male and 21 female) were studied, none of whom was on nonsteroidal anti‐inflammatory drugs or antibiotics. H. pylori infection was determined by rapid urease test (CLOtest), culture, antibody and RT‐PCR for Ure C, Cag A and 26 kDa gene and histology. Cytokine production of mucosal IL‐6 and IL‐8 were measured by ELISA. Results: Fifteen subjects were positive by CLOtest and/or bacterial culture. In these subjects histology showed numerous helical forms of H. pylori (Group I). Nine subjects were negative by CLOtest, bacterial culture, and mRNA for urease C fragment, but positive by PCR for the 26 kDa protein encoding gene. Histology in these subjects showed the presence of either coccoid forms (four), or scant helical forms (two), or mixed coccoid/helical forms (three) (Group II). Eleven subjects were negative by all methods of detection (Group III). IgG and IgA antibody levels in serum (p<0.05) and gastric tissue culture supernatant (p<0.001) were significantly higher in Group I than those in Group II or III. There were significant differences in the IgG serum and IgA supernatant antibody levels (p<0.01 and p<0.05) when Group II was compared to Group III. Supernatant IL‐6 levels were significantly higher in Group I (p<0.01) than those from Groups II and III. EL‐8 levels were higher in Group I (p<0.01) and Group II (p<0.05) when compared to Group III. Conclusions: ‘H. pylori‐negative’ gastritis can be associated with a non‐urease producing form of H. pylori, with a reduction in both local and systemic antibody levels and mucosal pro‐inflammatory cytokines.     

Toll样受体及其基因多态性与感染性疾病关系的研究进展

Toll样受体是近年来发现的跨膜信号传递受体,他作为一种重要的模式识别受体(PRRs)在先天免疫中通过对病原体相关的分子模式(PAMPs)的识别发挥作用,通过刺激信号的级联反应诱导炎症因子和细胞因子产生,在抗感染中起重要作用.基因多态性影响机体对疾病的遗传易感性,TLRs的位点多态性与炎性应答损伤和感染性疾病的遗传易感性相关.目前多数研究表明TLR4的Asp299Gly和Thr399Ile,TLR2的Arg753Gln和Arg667Trp多态性与感染性疾病的发生相关,其他TLRs的基因多态性也有研究.本文就TLRs家族的功能及其基因多态性与感染性疾病的关系作一综述.     

幽门螺杆菌慢性感染诱导胃上皮细胞产生凋亡耐受

目的：建立幽门螺杆菌（H.pylori)慢性感染胃上皮细胞模型,并分析H.pylori慢性感染与胃上皮细胞凋亡的关系。方法：首先用H.pylori SS1与人非肿瘤性胃上皮细胞株GES－1共培养16周,建立GES－1模型细胞,然后采用流式细胞术分析这种模型细胞对H.pylori和其它肠道细菌以及抗肿瘤药物凋亡诱导剂的应答。结果：成功获得了H.pylori慢性感染胃上皮细胞模型（GES－1模型细胞）。这种模型细胞不仅对H.pylori诱导的凋亡耐受,而且对其他肠道细菌和一些凋亡诱导剂也是耐受的。结论：幽门螺杆菌慢性感染诱导胃上皮细胞产生凋亡耐受,由此可能增加了胃上皮细胞癌变的危险性。