No allelic variant associations of the IL-1 and TNF gene polymorphisms in the susceptibility to duodenal ulcer disease

Recent studies have reported the association of a pro-inflammatory profile of genetic polymorphisms in IL-1B, IL-1RN, TNF-A, and IL-10 genes with an increased risk of non-cardia gastric cancer. Because gastric cancer and duodenal ulcer are mutually exclusive outcomes of Helicobacter pylori infection, we aimed to investigate possible allelic variant associations of several functional polymorphisms in the IL-1B, IL-1RN, TNFA, and LTA genes in the susceptibility to duodenal ulcer. Genomic DNA from 118 patients with duodenal ulcer and 97 healthy controls was typed for the IL-1B polymorphisms at positions -511, -31, and +3954, the VNTR polymorphism in intron 2 of the IL-1RN gene, the TNFA-308, TNFA -238, and the NcoI and BsI LTA polymorphisms by PCR, SSCP and TaqMan assays. H. pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs) use was investigated in patients and controls. Logistic regression analysis identified H. pylori infection (OR: 12.86; 95%CI: 3.85-43), NSAID use (OR: 11.95; 95%CI: 4.19-34.05), and family history-ulcer (OR: 3.79; 95%CI: 1.68-8.54) as independent risk factors for duodenal ulcer. When the effect of the combinations of IL-1 and TNF genotypes was studied we found that the distribution of all possible combinations of these eight polymorphisms was similar in duodenal ulcer patients and controls. The simultaneous carriage of alleles IL-1RN*2/IL-1B -31T/IL-1B -511C/IL-IB +3954C/TNF-HaplotypeE negative (termed in some studies as 'low-producing' alleles) was increased in H. pylori-positive duodenal ulcer patients compared to H. pylori-infected healthy controls (10.5% vs. 5.9%) although the difference did not reach statistical significance (OR: 1.85; 95%CI: 0.57-5.99, P = 0.41). Moreover, no differences were found with respect to H. pylori status, NSAID use, age, gender, smoking habit, type of complication, recurrence of the ulcer, and need for surgical treatment. Our data show no association between allelic variants of IL-1 and TNF gene polymorphisms in the susceptibility to and final outcome of duodenal ulcer.     

The polymorphic IL-1B and IL-1RN genes in the aetiopathogenesis of peptic ulcer

Besides environmental factors, the genetic background of an individual may contribute to the development and final outcome of peptic ulcer disease. Interleukin-1beta (IL-1beta) and the interleukin-1 receptor antagonist (IL-1ra) are cytokines that play a key role in modulating the inflammatory response in the gastrointestinal mucosa. This study aimed to investigate whether polymorphisms in the IL-1B and IL-RN genes are involved in the susceptibility to and final outcome of peptic ulcer disease. DNA from 179 unrelated Spanish Caucasian patients with peptic ulcer diseases and 99 ethnically matched healthy controls was typed for the TaqI polymorphism at position + 3954 in the IL-1B gene and the variable number of tandem repeats polymorphism in intron 2 of the IL-1RN gene. The determination of Helicobacter pylori status and non-steroidal anti-inflammatory drug (NSAIDs) use was studied in all patients and in controls. H. pylori infection and NSAID use were more frequent in ulcer patients than in controls. There were no significant differences in carriage rate, genotype and allele frequencies of the IL-1RN and the IL-1B(+3954) gene polymorphisms between peptic ulcer patients and controls. However, a strong allelic association between IL-1B and IL-1RN genes was found in duodenal ulcer patients (P < 0.0006). Logistic regression identified H. pylori infection and NSAIDs use as independent risk factors for peptic ulcer diseases whereas the simultaneous carriage of IL-1B(+3954) allele 2 and IL-1RN allele 2 was associated with reduced risk for duodenal ulcer disease (OR: 0.37, 95% CI = 0.14-0.9). Our data suggest that IL-1B and IL-1RN genes in addition to bacterial and environmental factors play a key role in determining the final outcome of peptic ulcer disease.     

Associations of the IL-1 and TNF gene polymorphisms in the susceptibility to duodenal ulcer disease in Chinese Han population

Our aim was to investigate whether genetic polymorphism of IL-1Β-511, IL-1RN, TNF-A-308 are involved in the susceptibility to duodenal ulcer (DU). 437 unrelated Chinese Han patients with DU and 148 healthy controls were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method for the IL-1B-511, TNF-A-308 gene polymorphisms and the VNTR polymorphism in intron 2 of the IL-1RN gene polymorphisms. There was no difference in the genetic polymorphism of IL-1Β-511, IL-1RN and TNF-A-308 in the patients with DU compared with control. After stratified by Helicobacter pylori infection, they also could not reach significant differences in this study. No statistically significant differences were observed in DU group compared with control according to combination of the IL-1Β-511 and IL-1RN genotypes regardless of H. pylori positivity. These findings show that no evidence for the involvement of a proinflammatory polymorphism in the IL-1Β-511, IL-1RN and TNF-A-308 in the susceptibility to DU in China.     

Influence of IL-1 gene cluster polymorphisms on the development of H. pylori associated gastric ulcer

BACKGROUND AND AIMS: Chronic H. pylori infection is the main cause of ulcer disease which depicts a major burden of our healthy care systems. The individual host immune response plays a pivotal role in the outcome of the infection but genetic susceptibility to develop gastric ulcer is unknown. IL-1beta and its natural receptor antagonist IL-1ra are involved in the inflammatory response to H. pylori infection. Thus, we investigated the influence of functional genetic variants in the IL-1 gene cluster on the development of gastric ulcer disease. PATIENTS AND METHODS: 390 H. pylori infected patients were genotyped for IL-1B -31 and +3954 by TaqMan technology. Alleles of IL-1RN 86VNTR were determined by gel electrophoresis after amplification. Three hundred and sixty healthy blood donors were included as healthy controls. RESULTS: Carriage of the IL-1B -31 C allele conferred a increased but not significant risk for H. pylori infection (OR: 1.3, Wald 95% CI: 0.8相似文献   

Association of interleukin-1B and interleukin-1RN polymorphisms with gastric cancer in a high-risk population of Costa Rica

Abstract Several risk factors have been associated with gastric cancer, among them Helicobacter pylori infection. This bacterium yields inflammation, the degree of which depends on the bacterial strain and the severity of the host response. The inflammatory response involves a complex cytokine network. Recently, polymorphisms of the genes coding for interleukin-1β (IL-1B), interleukin-1Ra (ILRN) and interleukin-10 have been associated with an increased risk of gastric cancer. In order to determine the association of the IL-1B, IL-1RN and IL-10 polymorphisms with gastric cancer in a high-risk Costa Rican population, we analysed purified DNA of 58 gastric cancer patients, 99 controls and 41 patients classified as group I or II, according to the Japanese classification. Genotyping was carried out by PCR, PCR-RFLP and pyrosequencing analysis. We did not find any association of the IL-1B-31, IL-1B-511 and IL-10 polymorphisms with the risk for developing gastric cancer in the studied population. Carriers of the IL-1B+3954T/– had an increased risk for developing gastric cancer (OR 3.7; 95%CI: 1.34–10.2). Also we found an increased risk for developing gastric cancer for allele 2 heterozygotes of the IL-1RN (OR 2.94; 95%CI: 1.09–7.93). This is the first time that IL-1B+3954 has been associated with gastric cancer. This is one of the first studies trying to describe the role played by IL-1B, IL-1RN and IL-10 genetic polymorphisms in gastric cancer in one of the highest risk American countries. Further investigation on American countries is needed.     

Association of interleukin-1beta and interleukin-1 receptor antagonist polymorphisms with bacterial vaginosis in non-pregnant Italian women

Bacterial vaginosis (BV) is the most prevalent alteration of vaginal microflora worldwide. BV is a polymicrobial disorder, and its etiology is elusive. Factors predisposing to this recurrent condition are not fully characterized. We aimed to investigate whether interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1ra) polymorphisms are associated with BV in non-pregnant white Italian women. Genomic DNA was obtained from 164 BV positive, and 406 control women. Two diallelic polymorphisms in the IL-1beta gene (IL-1B) representing C/T base transitions at - 511 and + 3954 positions and a variable number tandem repeats (VNTR) in intron 2 of the IL-1ra gene (IL-1RN) were assessed. We demonstrated that women who were homozygous for - 511 CC or + 3954 TT of the IL-1B gene were at increased risk for BV with an odds ratio (OR) = 1.5 [95% confidence interval (CI) = 1.03-2.14, P = 0.032], and OR = 2.8 (95% CI = 1.37-5.88, P = 0.004), respectively. The haplotype - 511/ + 3954 T-C was protective for BV, with an OR = 0.7 (95% CI = 0.49-0.90, P = 0.009). The IL-1RN VNTR genotype was not associated with BV, although the rare allele 3 showed a trend towards protection (P = 0.049). These data show that host genetic variants at the IL-1beta locus predispose to BV among Caucasian non-pregnant women. Further studies will determine whether these genetic polymorphisms modulate the risk for BV recurrence, and/or BV associated severe adverse outcomes as preterm birth and human immunodeficiency virus transmission.     

Interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) gene polymorphisms are not associated with tubal pathology and Chlamydia trachomatis-related tubal factor subfertility

BACKGROUND: Chlamydia trachomatis infections have been associated with tubal pathology. However, not all C.trachomatis-infected women actually develop tubal pathology. Recently, host genetic factors such as the interleukin-1 gene cluster have been linked to inflammatory and infectious diseases. METHODS: Dutch Caucasian women were investigated for (i) the role of interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) gene polymorphisms in tubal pathology (group 1); and (ii) the presence of these gene polymorphisms in C.trachomatis IgG-positive women with and without tubal pathology (group 2). Group 1 consisted of women with (n = 40) or without (n = 95) tubal pathology, respectively, and group 2 of C.trachomatis IgG-positive women of whom 28 had tubal pathology at laparoscopy and 47 did not. IL-1B-511 and IL-1B+3954 gene polymorphisms were assessed by PCR-restriction fragment length polymorphism (RFLP), and the variable number of tandem repeats (VNTR) of the IL-1RN gene were assessed by a PCR-based assay. RESULTS: Neither IL-1B-511, IL-1B+3954 nor IL-1RN genotypes, allele or carrier frequencies showed significant association with tubal pathology or C.trachomatis post-infection-based tubal pathology. CONCLUSIONS: The data obtained suggest that specific IL-1 gene polymorphisms are not associated with the tubal pathology risk or to the development of C.trachomatis-based post-infectious severe sequelae.     

IL-1 gene polymorphisms and genetic susceptibility of gallbladder cancer in a north Indian population

Long-standing gallstones are generally present in 65-80% patients of gallbladder cancer (GBC). It has also been suggested that inflammation caused by gallstones may be involved in the development of GBC. Interleukin-1 receptor antagonist (IL-1RN) and interleukin-1 beta (IL-1B) are proinflammatory cytokine genes at the interleukin-1 locus, and polymorphisms of these genes have been associated with various inflammatory diseases. The aim of this study was to investigate whether polymorphism in the IL-1RN and IL-1B genes are associated with GBC patients with and without gallstones. Polymorphisms within the IL-1RN 86-base pair VNTR (variable number tandem repeat) and IL-1B (-511C --> T) were genotyped using polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism in 166 healthy subjects and 124 GBC patients. The frequency of the IL-1RN, VNTR 2/2 genotype was significantly higher in GBC patients [P = 0.017; odds ratio (OR) = 3.25; 95% confidence interval (CI) = 1.23-8.58]. CC genotype and 'C' allele of the -511IL-1B C --> T polymorphism also showed high risk for GBC (P = 0.033; OR = 3.36; 95%CI = 1.52-7.43, P = 0.047, OR = 1.41; 95%CI = 1.00-1.98, respectively). The higher cancer risk due to the IL-1RN, 2/2 genotype was observed in GBC patients with or without stones (P = 0.038; OR = 3.58; 95%CI = 1.08-11.65, P = 0.035; OR = 3.33; 95%CI = 1.08-10.61). Risk due to the CC genotype of IL-1B, however, was confined to GBC patients harboring gallstones (P = 0.0003; OR = 6.92; 95%CI = 2.65-18.03). The haplotype 1/C of IL-1RN and IL-1B was found to confer a significantly enhanced risk of GBC in cancer patients with gallstones (P = 0.022; OR = 2.19; 95%CI = 1.12-4.27), while higher risk resulting from 2/C haplotype was of borderline significance (P = 0.061; OR = 3.04; 95%CI = 0.95-9.70). Individuals with 1/C and 2/C haplotypes of IL-1RN VNTR and -511IL-1B C --> T polymorphisms were more susceptible to develop GBC with gallstones compared to healthy controls in north India.     

IL-1B基因多态性和H.pylori感染与汉族人胃癌的相关性研究

目的：通过比较胃癌患者与匹配人群的幽门螺旋杆菌（Helicobacter pylori，H.pylori）感染率和IL-1B基因多态性，探讨IL-1B基因多态性是否增加H．pylori感染后胃癌发生的危险性。方法：采用聚合酶链反应-限制性片段长度多态性（Restriction fragment length polymorphism，RFLP）分析法检测胃癌低发区84例胃癌患者和84例与之性别、年龄匹配的普通人群的1L-1B基因多态性。采用酶联免疫吸附法（Enzyme—linked immunosorbent assay，ELISA）检测上述人群中的H.pylori感染率。结果：①胃癌患者IL-1B-511T／T基因型频率显著高于性别、年龄匹配的对照人群（P〈0．05），IL-1B-31T／T基因型频率在两组间无显著差异（P〉0．05）。84例胃癌患者的H.pylori感染率显著高于对照人群（P〈0．01）。胃癌患者H.pylori阳性感染者IL-1B-511 T／T基因型个体显著多于对照人群。结论：H.pylori感染者胃癌组织中IL-1B-511 T／T基因型为主，提示IL-1B-511 T／T基因型可能增加H.pylori感染后中国汉族人群发生胃癌的危险性，而IL-1B-31基因型与H.pylori感染后中国汉族人群胃癌发生无显著相关性。     

IL-1β血清水平及IL-1B和IL-1受体拮抗剂基因多态性与胃癌关系探讨

目的 探讨白细胞介素(IL)-1β血清水平及IL-1B和IL-1RN基因多态性与胃癌及幽门螺杆菌(Hp)感染胃癌发生发展的相关性.方法 以酶联免疫吸附试验(ELISA)测定IL-1β血清水平及抗Hp抗体IgG、IgM和IgA浓度;采用基因芯片技术检测260例胃癌患者和284例不相关联的健康对照人群中IL-1B-31C/T、-511C/T位点单核苷酸多态性(SNP);以琼脂糖凝胶电泳检测IL-1RN基因多态性(VNTR).结果 胃癌组IL-1β血清水平[(802±148) ng/L]显著高于对照组[(501±125) ng/L],P<0.01;胃癌组Hp感染率明显高于对照组[P<0.001, 相对危险度(OR)=2.59].胃癌组IL-1B-31TT基因型频率明显高于对照组(P<0.01,OR=1.95);胃癌组IL-1B-511TT基因型频率明显高于对照组(P<0.05,OR=1.62);Hp阳性(Hp+)胃癌组-511TT基因型频率明显高于Hp阴性(Hp-)胃癌(P<0.05,OR= 2.00);胃癌组T-T单体型频率显著高于对照组(χ2=4.45,P<0.05).不论在胃癌组还是在Hp+胃癌组,携带IL-1B-31T或-511T等位基因者血清IL-1β水平均高于其相应CC基因型携带者,且IL-1B-31T、-511T携带者在Hp+胃癌组较Hp-胃癌组的IL-1β水平显著增高(P<0.001).未见IL-1RN基因型及其他IL-1B基因型与胃癌或Hp+胃癌有显著相关性.结论 IL-1B-31TT基因型与胃癌易感性相关;IL-1B-511TT基因型与胃癌特别是Hp+胃癌易感性相关.IL-1B-31T/-511T等位基因均与IL-1β血清水平显著相关(P<0.001).T-T单体型可能是胃癌的遗传易感因素.     

TGFB1 gene polymorphisms: their relevance in the susceptibility to Helicobacter pylori-related diseases

Recent studies have revealed elevated expression of transforming growth factor beta1 (TGF-beta1) in gastric mucosa of patients with gastric cancer (GC) and those undergoing ulcer repair. As production of TGF-beta1 is genetically regulated, we aimed to assess whether functional polymorphisms of the TGFB1 gene are involved in susceptibility to and clinical characteristics of Helicobacter pylori-related diseases. DNA from 142 unrelated Spanish patients with GC, 200 with peptic ulcer and 342 healthy controls was typed for the MspA1I T+869C, and the Sau96I G+915C polymorphisms of the TGFB1 gene using polymerase chain reaction and RFLP analysis. H. pylori infection and CagA/VacA antibody status were determined by Western blot in patients and controls. H. pylori infection (odds ratio (OR): 11.44; 95% confidence interval (CI): 4.45-29.42; P<0.001) and non-steroidal anti-inflammatory drugs (OR: 5.07; 95% CI: 2.53-10.16; P<0.001) were identified as independent risks factors for duodenal ulcer (DU), whereas the TGFB1+869(*)C/C genotype was associated with reduced risk of developing the disease (OR: 0.32; 95% CI=0.15-0.68; P=0.003). Our results show that the TGFB1 T+869C gene polymorphism is involved in the susceptibility to DU and provide further evidence that host genetic factors play a key role in the pathogenesis of H. pylori-related diseases.     

Association of IL-1 gene complex members with ankylosing spondylitis in Chinese Han population

There are reports of IL-1 complex gene polymorphisms in ankylosing spondylitis (AS; MIM 106300), but the results have been inconsistent among populations. Moreover, few studies examine the association between IL-1 complex gene polymorphisms and clinical symptoms of AS patients. We investigated polymorphisms of IL-1 complex with AS in the Chinese Han population in this study. Chinese Han AS patients and ethnically matched healthy controls were genotyped for five single nucleotide polymorphisms (IL1β+3953, β-511, F10.3, RN.4, RN.6/1) and the IL1RN.VNTR of IL-1 gene cluster. Allele, Genotype and haplotype frequencies were compared between cases and controls by SHEsis software. The frequency of allele C of the marker IL1F10.3 was significantly increased in AS patients versus controls [p = 0.001, odds ratio (OR) = 1.54, 95% confidence interval (CI) = 1.19–1.20; p = 0.002, respectively]. Strong linkage disequilibrium was identified between IL1B-511, IL1B+3953 and RN4 in both patients and healthy controls (D′ > 0.95). Haplotypes of pairs of these markers (6) were also significantly associated with AS. The strongest associations observed was between allele combination B-511-T/B+3953-C/F10.3-C/RN4-T/RN2VNTR-1/RN6.1-C and AS (p = 3.32 × 10⁻⁵, OR = 4.41, 95% CI=2.1–9.3). Clinical manifestation showed week association between RN2VNTR A2 allele and risk of peripheral arthritis (OR = 0.2, 95% CI = 0.07–0.91). The IL-1 gene cluster is associated with AS in Chinese population. This finding provides strong statistical support for the previously observed relationship and indicates possible association between clinical manifestation and genetic factor.     

IL-1B-511单核苷酸多态性与我国胃癌高发区胃黏膜萎缩关系的研究

目的： 研究我国胃癌高发区IL-1B-511基因多态性、幽门螺杆菌(Hp)感染与胃黏膜萎缩的关系。方法： 研究对象为胃癌高发区（陕西）健康志愿者500例，人群按照年龄分成20-29岁、30-39岁、40-49岁、50-59岁、60岁以上等5组，每组100例。IL-1B-511基因多态性的分析采用限制性片段长度多态性（PCR-RFLP）方法，以血清胃蛋白酶原Ⅰ（PGⅠ）浓度和PGⅠ/PGⅡ比值作为胃黏膜萎缩的指标，血清PGⅠ、PGⅡ浓度和抗Hp-IgG抗体的检测均采用酶联免疫吸附试验（ELISA）检测。结果： 随着年龄的增长，血清PGⅠ的浓度与 PGⅠ/PGⅡ 的比值呈逐渐下降的趋势；在各年龄组中，IL-1B-511 T/T基因型Hp阳性者其血清PGⅠ及PGⅠ/PGⅡ低于相应年龄组Hp阴性者（P<0.05）；多因素回归分析提示“IL-1B-511 T/T基因型”、“年龄段”和“Hp”对“PGⅠ/PGⅡ比值”有显著影响 (P<0.05、P<0.05和P<0.01)。结论： 我国胃癌高发区胃黏膜萎缩的发生与IL-1B-511 T/T基因型、年龄和Hp感染有密切关系，IL-1B-511 T/T基因型增加Hp感染后胃黏膜萎缩发生的危险性。     

C-reactive protein levels and common polymorphisms of the interleukin-1 gene cluster and interleukin-6 gene in patients with coronary heart disease.

C-reactive protein (CRP) is an inflammatory marker associated with increased cardiovascular risk. Production of CRP is regulated by interleukin (IL)-1beta, IL-1 receptor antagonist and IL-6. In 160 patients with coronary heart disease (CHD) confirmed by angiography, we examined the relationship between CRP level and five polymorphisms in genes coding for these cytokines: IL-1B(-511), IL-1B(+3954), a variable number tandem repeat (VNTR) polymorphism in intron 2 of IL-1RN [IL-1RN(VNTR)], IL-6(-174) and IL-6(-572). CRP values were logarithmically normalized (log-CRP) for statistical calculations. In univariate analysis, carrier status for the IL-1B(+3954)T allele and IL-1RN(VNTR) allele 2 [IL-1RN(VNTR)*2] correlated with higher (P < 0.01) and lower (P < 0.05) log-CRP values, respectively. Among the potential confounding factors analysed, smoking, body mass index, total cholesterol (P < 0.05 for all) and diabetes (P = 0.056) were positively correlated with CRP level. After adjustment for non-genetic covariates, CRP levels remained significantly (P < 0.01) higher in carriers of IL-1B(+3954)T than in non-carriers: mean log-CRP (with 95% confidence interval) was 0.443 (0.311-0.574) for CT or TT genotypes compared with 0.240 (0.107-0.373) for the CC genotype, which corresponded to back-transformed CRP levels of 2.77 and 1.74 mg l(-1), respectively. Adjusted association was also significant for IL-1RN(VNTR)*2 (P < 0.01), with lower CRP levels in the presence of allele 2: the mean log-CRP value was 0.252 (0.115-0.388) for carriers and 0.421 (0.290-0.552) for non-carriers (CRP 1.79 and 2.64 mg l(-1), respectively). When alleles of both polymorphisms were entered into the model simultaneously, the association remained significant for IL-1B(+3954)T (P < 0.05), but not for IL-1RN(VNTR)*2. We conclude that IL-1B(+3954)T is associated with higher CRP levels in patients with CHD, and we found that this association was significant after adjustment for major risk factors. Our data also suggest a possible relationship of IL-1RN(VNTR)*2 with lower CRP levels in the same patients.     

白细胞介素1B及受体拮抗剂基因多态性与慢性乙型肝炎的相关性

目的　探讨白细胞介素 1B(interlukin- 1B,IL - 1B)基因启动子区域 - 5 11C/ T和白细胞介素1受体拮抗剂 (receptor antagonist,RN )基因在慢性乙型肝炎及正常人群中的多态性 ,初步分析其基因型与慢性乙型肝炎的相关性。　方法　对 190例慢性乙型肝炎患者和 2 4 9名正常人 IL - 1B、 RN基因进行PCR扩增 ,其中 IL - 1B基因用 Ava 限制性内切酶对 PCR产物进行消化 ,然后经琼脂糖凝胶电泳分别对IL- 1B、RN基因多态性进行分析。　结果　 IL- 1B基因在正常人和慢性乙型肝炎患者中 - 5 11C等位基因频率分别为 0 .5 0和 0 .4 8,- 5 11T等位基因频率分别为 0 .5 0和 0 .5 2。 3种基因型频率分别为 CC型 :0 .2 6(6 5 / 2 4 9)和 0 .2 4 (4 5 / 190 ) ;CT型 :0 .4 7(118/ 2 4 9)和 0 .4 9(94 / 190 ) ;TT型 :0 .2 7(6 6 / 2 4 9)和 0 .2 7(5 1/190 )。IL- 1B基因启动子 - 5 11位点 CC型慢性乙型肝炎患者乙肝病毒 DNA水平明显降低 (P<0 .0 5 )。在IL- 1RN的 5种不同组合等位基因 ,只发现 1/ 1、1/ 2、2 / 2和 1/ 4四种基因型 ,其在慢性乙型肝炎患者和正常人中的分布为 1/ 1型 :0 .88和 0 .81;1/ 2型 :0 .0 9和 0 .16 ;2 / 2型 :0 .0 1和 0 .0 1;1/ 4型 :0 .0 2和 0 .0 2。其中 IL - 1RN* 1等位基因频率在慢性乙型肝     

Decreased epithelial cytokine responses in the duodenal mucosa of Helicobacter pylori-infected duodenal ulcer patients

Helicobacter pylori colonizes the human stomach and areas of gastric metaplasia in the duodenum, but only a minority of those that are infected develop symptoms, e.g., peptic ulcers. Although most ulcers occur in the duodenum, almost all studies of mucosal immune responses against the infection have been limited to responses in the stomach. In the present study we evaluated whether there are differences in the levels of proinflammatory cytokines as well as immunoregulatory cytokines in the duodenal mucosa of duodenal ulcer (DU) patients and asymptomatic (AS) carriers which may be related to the development of duodenal ulcers. Duodenal biopsy specimens collected from normal mucosa as well as metaplastic mucosa of DU patients, AS carriers, and uninfected controls were analyzed for a number of cytokines by immunohistochemistry. Interestingly, the level of epithelial staining for several cytokines, e.g., interleukin-8 (IL-8), transforming growth factor beta (TGF-beta), and gamma interferon (IFN-gamma), was found to be significantly lower in DU patients than in AS carriers and uninfected individuals. No differences were observed when cytokine staining in normal and metaplastic biopsy specimens was compared. However, larger numbers of IL-8-, IL-6-, TGF-beta-, and IFN-gamma-positive mononuclear cells were observed in the duodenal lamina propria of both DU patients and AS carriers than in that of the uninfected controls. Our finding that a number of cytokines that may be important for the mucosal host defense against H. pylori are strongly decreased in the duodenal epithelium of ulcer patients suggests that a down-regulated immune response plays a role in the development of duodenal ulcers.     

Interleukin-1 gene cluster polymorphism in chagas disease in a Colombian case-control study

The aim of this study was to assess the possible association between the IL1A, IL1B and IL1RN gene polymorphisms and Chagas disease. Our study population consisted of 130 serologically positive cardiomyopathic patients and 130 seropositive and asymptomatic individuals from a Colombian population where Trypanosoma cruzi infection is endemic. Genotyping of the IL1A (-889C/T, +4845G/T), IL1B (-511C/T, -31T/C, +3954T/C, +5810G/A) and IL1RN (+8006T/C, +8061C/T, +11100T/C) polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction sequence-specific primer methods. Statistically significant differences in the distribution of the IL1B +5810 genotypes were observed comparing cardiomyopathic patients and asymptomatic individuals (p = 0.036). Frequency of the GG genotype was higher in the cardiomyopathic patient group than in the asymptomatic group (13% versus 5%, p = 0.03, odds ratio [OR] = 2.64, 95% confidence interval [CI] = 0.99-7.33). Differences in the distribution of the allele frequencies were also observed, being the +5810G allele overrepresented in patients with cardiomyopathy (37% versus 27%, p = 0.014, OR = 1.59, 95% CI = 1.08-2.36). Examination of markers in the IL1A (-889 and +4845), IL1B (-511, -31, and +3954) and IL1RN (+11100) genes revealed that the overall distribution of alleles and genotypes in patients with chagasic cardiomyopathy and asymptomatic were not significantly different. Our results show that in Colombian population the IL1B+5810G allele was associated with an increased risk chagasic cardiomyopathy. In addition, we demonstrated that homozygosity for the IL1B +5810G risk allele increased significantly the susceptibility to cardiomyopathy. This implies that the effect of IL1B gene on chagasic cardiomyopathy predisposition is dose dependent. We found that the haplotype CT of IL1B -31 and +3954 polymorphisms showed higher association with risk to chagasic cardiomyopathy (p(c) = 0.008, OR = 12.53) and the extended haplotype (CCTCATT) was significantly more frequent in asymptomatic than in cardiomyopathic patients (p = 0.0014, p(c) = 0.011, OR = 0.17). Therefore this study suggests that IL1 gene cluster polymorphisms may play a relevant role in the susceptibility to development of chagasic chronic cardiomyopathy.     

Differences in surface-exposed antigen expression between Helicobacter pylori strains isolated from duodenal ulcer patients and from asymptomatic subjects

We have analyzed possible qualitative and quantitative differences in antigen expression between Helicobacter pylori strains isolated from the antrum and different locations in the duodenum of 21 duodenal ulcer (DU) patients and 20 asymptomatic subjects (AS) by enzyme-linked immunosorbent assay (ELISA) and inhibition ELISA. Almost all antral and duodenal strains grown in vitro expressed the N-acetyl-neuroaminyllactose-binding hemagglutinin, flagellins (subunits FlaA and FlaB), urease, a 26-kDa protein, and a neutrophil-activating protein. In 75% of both the DU patients and the AS, antral H. pylori strains expressed either the blood group antigen Lewis y (Le(y)) alone or together with the Le(x) antigen. However, duodenal H. pylori strains of DU patients expressed Le(y) antigen more frequently than corresponding strains of AS (P < 0.05). Presence of Le(y) on H. pylori was related to the degree of active duodenitis (P < 0.05). Duodenal H. pylori strains isolated from AS were significantly more often Lewis nontypeable than duodenal strains of DU patients (P < 0.01). Presence of H. pylori blood group antigen-binding adhesin (BabA) was significantly higher on both antral and duodenal strains isolated from DU patients than on corresponding strains isolated from AS (P < 0.05). BabA-positive duodenal H. pylori strains isolated from DU patients were associated with active duodenitis more frequently than corresponding strains isolated from AS (P < 0.01). Infection with H. pylori strains positive for Le(y) and BabA in the duodenum is associated with development of duodenal ulcer formation.