Association of interleukin 1 gene family polymorphisms with duodenal ulcer disease

Cytokine genes taking part in the immunological response to Helicobacter pylori infection are good candidates to study for genetic predisposition to duodenal ulcer disease (DU). Among cytokines, interleukin (IL)-1beta and its natural specific inhibitor, the interleukin-1 receptor antagonist, are cytokines that play a key role in regulating gastric acid secretion and modulating the immune response in the gastrointestinal mucosa. We aimed to investigate whether polymorphisms in the IL-1B and IL-1RN genes are involved in the susceptibility to duodenal ulcer. DNA from 131 unrelated Spanish Caucasian patients with DU and 105 ethnically matched healthy controls was typed for the IL-1B-511, IL-1B-31, and IL-1B + 3954 gene polymorphisms, and the VNTR polymorphism in intron 2 of the IL-1RN gene by polymerase chain reaction (PCR)-based methods and TaqMan assays. H. pylori status and non-steroidal anti-inflammatory drugs (NSAIDs) use was determined in all patients and controls. Logistic regression analysis identified H. pylori infection (OR: 9.74; 95%CI = 3.53-26.89) and NSAIDs use (OR: 8.82; 95%CI = 3.51-22.17) as independent risk factors for DU. In addition, the simultaneous carriage of IL-1RN*2, IL-1B-511*C, IL-1B-31*T and IL-1B + 3954*C alleles was a genetic risk factor for DU in patients with H. pylori infection (OR: 3.22; 95%CI = 1.09-9.47). No significant differences in IL-1RN and IL-1B genotypes were found when patients were categorized according to gender, age of onset, smoking habit, NSAIDs use, type of complication and positive family history. Our results provide further evidence that host genetic factors play a key role in the pathogenesis of duodenal ulcer.     

IL-1B and IL-6 gene polymorphisms encode significant risk for the development of recurrent aphthous stomatitis (RAS)

Recurrent aphthous stomatitis (RAS) is an, ulcerative condition of the mouth, with a polygenic mode of inheritance in which cytokines are thought to play an important role. Ninety-one RAS patients and 91 controls were genotyped for known IL-1A, IL-1B, IL-1RN and IL-6 gene polymorphisms. Inheritance of the G allele of the IL-1B -511 polymorphism was strongly associated with RAS (OR = 2.5, P < 0.00002), with increased numbers of G/G homozygotes (OR = 4.5, P < 0.0005). The G allele of IL-6 -174 also occurred more frequently in RAS (OR = 2.6, P < 0.0001) with greatest risk associated with G/G homozygosity (OR = 3.4, P < 0.0001). IL-1RN VNTR 1/1 homozygotes also occurred more frequently in RAS (OR = 2.0, P < 0.02). Inheritance of the G/G genotype of both IL-1B and IL-6 was a particularly strong predictor for RAS (OR = 8.5).     

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.     

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.     

白细胞介素-1基因多态性与高血压易感性的研究

目的　观察白细胞介素 - 1(interleukin- 1,IL- 1)基因多态性在中国汉族人群中的分布及其与原发性高血压 (essential hypertension,EH)的关系 ,初步分析其基因型与 EH易感性的相关性。方法　应用聚合酶链反应和限制性片段长度多态性的方法 ,检测湖北省汉族 15 2例 EH患者和 16 8名正常对照者的IL- 1基因多态性 ,包括 IL- 1α(- 889C/ T)位点、IL- 1β(- 5 11C/ T)位点、IL- 1β( 395 3C/ T)位点、IL- 1Ra( 80 0 6 T/ C)位点多态性以及 IL- 1Ra第 2内含子可变数串联重复序列多态性。结果　IL- 1α(- 889C/ T)位点、IL- 1β( 395 3C/ T)位点、IL- 1Ra( 80 0 6 T/ C)位点多态性和 IL- 1Ra可变重复序列多态性在 EH组和正常人群中的分布差异无显著性 (P>0 .0 5 ) ,而 IL- 1β(- 5 11C/ T)位点多态性在两组人群中的分布差异存在显著性 (P<0 .0 5 ) ,携带 CT基因型罹患 EH的危险性可增加 2 .5 4倍。结论　 IL- 1β基因启动子区 - 5 11位点 C/ T多态性可能与 EH易感性存在相关关系。     

Role of genetic variant A-204C of cholesterol 7alpha-hydroxylase (CYP7A1) in susceptibility to gallbladder cancer

Gallbladder carcinoma (GBC) usually arises in the background of gallstone disease. Cholesterol 7alpha-hydroxylase (CYP7A1) is a rate-limiting enzyme for cholesterol catabolism and bile acid synthesis. A-204C genetic polymorphism in CYP7A1 may influence gene expression and thus affect the risk of gallstone disease and GBC. We aimed to study the association of A-204C variation of CYP7A1 gene promoter polymorphism in GBC patients, gallstone patients and healthy subjects. The study included 141 histopathologically proven GBC patients, ultrasonographically proven 185 symptomatic gallstone patients and 200 gallstone-free healthy subjects. Genotyping was done by PCR-RFLP method. CYP7A1 A-204C genotypes in control population were in Hardy-Weinberg equilibrium. The CC genotype conferred marginally significant risk for gallstone disease (p=0.051; OR=1.54; 95% CI=0.9-3.4). In GBC patients, the CYP7A1 A-204C polymorphism conferred high risk for GBC at genotype (p=0.005; OR=2.78; 95% CI: 1.3-5.6) as well as allele levels (p=0.008; OR=1.58 and 95% CI: 1.1-2.2). After stratification of GBC patients on the basis of presence or absence of gallstones, CC genotype imparted higher risk for GBC without stones (p=0.002; OR=4.44: 95% CI=1.7-11.3). The association of the polymorphism with GBC was more pronounced in female GBC patients, and also in cancer patients who developed GBC at advanced age. The CC genotype of CYP7A1 is an independent genetic risk factor for GBC but plays a modest role in susceptibility to gallstone disease. The GBC pathogenesis by CYP7A1 polymorphism appears to be independent of gallstone pathway and probably involves genotoxicity due to lipid peroxidation mechanisms.     

Genetic analysis of interleukin-1 receptor antagonist and interleukin-1β single-nucleotide polymorphisms C−511T and C+3953T in alopecia areata: susceptibility and severity association

The present study was aimed to explore the effect of two selected polymorphisms from interleukin-1β (IL-1β) gene [SNPs ?511 and +3953] and a variable number of tandem repeat (VNTR) from interleukin-1 receptor antagonist (IL-1RN) on the susceptibility and severity of alopecia areata (AA) in Kuwaiti subjects. IL-1β SNPs C?511T, C+3953T, and IL-1RN VNTR were screened in 96 alopecia patients classified clinically, according to the disease severity as patchy (P), semiuniversalis (SU), and universalis (U), and in 100 ethnically matched healthy controls. Polymerase chain reaction followed by restriction fragment length polymorphism and direct DNA sequencing were employed for genotyping. Comparing the stratified AA cases based on severity, IL-β SNP C?511T showed a significant association (genotype and allelotype levels p = 0.03 and p = 0.028, respectively). Genotype CC was 50 % more frequent in U cases than in P or SU. When P and SU were grouped and tested against U, a significant difference was observed (genotype and allelotype levels p = 0.006 and p = 0.008, respectively). Compared to genotype CT, carriers of IL-1β ?511 CC genotype showed an increased risk to develop severe AA (p = 0.004, OR = 4.14, 95 % CI = 1.61–10.69). Four alleles and genotypes (1/1, 1/3, 1/4, and 2/2) of IL-1RN VNTR were detected in AA patients while only two (1/1 and 1/3) in controls. IL-1RN VNTR showed genotype and allelotype association with AA (p = 0.05 and p = 0.025, respectively). Our results showed that IL-1β and IL-1RN VNTR are significantly associated with the susceptibility to alopecia areata. Allele C of the IL-β C?511T SNP is linked to the severe form of AA.     

Genetic susceptibility of epidermal growth factor +61A>G and transforming growth factor beta1 -509C>T gene polymorphisms with gallbladder cancer

Epidermal growth factor (EGF) and transforming growth factor beta1 (TGFbeta1) play important roles in tumor biology. Single nucleotide polymorphisms in EGF and TGFB1 genes alter the expression of these growth factors and influence the tumorigenesis process. The aim of our present study was to determine the association of EGF+61A>G (rs4444903) and TGFB1-509C>T (rs1800469) gene polymorphism with susceptibility to gallbladder cancer (GBC). The present case-control association study was carried out in 126 confirmed GBC patients and 190 healthy subjects. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism methods. The GG genotype of EGF+61A>G was significantly associated with GBC [p=0.012, odds ratio (OR)=2.22, 95% confidence interval (CI)=1.19-4.15] in comparison to healthy subjects. Analysis based on gender indicated risk due to GG genotype was limited to female GBC patients (p=0.003, OR=3.45, 95% CI=1.52-7.82). Upon stratification of GBC patients on the basis of the presence or absence of gallstones, the risk due to EGF polymorphism was not modulated by the status of gallstones. The TGFB1-509C>T polymorphism was not associated with GBC. Also, we did not find any association of this polymorphism when GBC patients were subdivided on the basis of gender. However, after stratification of GBC patients on the status of gallstones, we determined that the CT genotype of TGFB1 was associated with increased risk of GBC without gallstones (p value=0.030, OR=2.90, 95% CI=1.26-6.69). Furthermore, the combination of the GG genotype of EGF and the CT genotype of TGFB1 demonstrated synergistic increase in risk of GBC.In conclusion, the higher producing +61G allele of EGF and -509 CT genotype of TGFB1 synergistically increase the susceptibility of gallbladder cancer (p value=0.003). Further study in large samples size is required to confirm our findings.     

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.     

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.     

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.     

Potential influence of interleukin-1 haplotype IL-1 beta-511*T-IL-1RN*1 in conferring low risk to middle third location of esophageal cancer: a case-control study

Interleukin (IL)-1 gene polymorphisms affect several inflammatory diseases, including cancer. Therefore, we studied genetic association of biallelic (-511C>T) polymorphism of IL-1β and 86-bp VNTR polymorphism of IL-1RN in 159 patients with esophageal cancer (EC) and 194 age- and gender-matched healthy controls. Genetic analysis for IL-1 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of IL-1β (-511C>T) and IL-1RN (variable number tandem repeat) genotypes, alleles, and haplotypes did not differ significantly between patients and controls. However, IL-1β -511TT genotype and T1+ haplotype combination illustrated low risk for disease at the middle third location of the tumor (odds ratio [OR] = 0.27; 95% confidence interval [CI] = 0.11–0.62; p = 0.002; OR = 0.462; 95% CI = 0.253–0.845, p = 0.01). In conclusion, subjects with IL-1β -511TT genotype or IL-1β*T-IL-1RN*1 (T1) haplotype had lower risk for middle third tumor location of EC in a northern Indian population.     

The interleukin 1B-511 polymorphism is associated with the risk of developing restenosis after coronary stenting in Mexican patients

Inflammation is the primary response to vessel wall injury caused by stent placement in coronary arteries. Cytokines of the interleukin-1 family are central regulators in immunoinflammatory mechanisms. The objective of this study was to test for association between IL-1 family gene polymorphisms and risk for restenosis after coronary stent placement. The IL-1B-511, IL-1F10.3, RN.4T>C, RN.6/1C>T, RN.6/2C>G, and IL-1RN VNTR polymorphisms were analyzed by 5' exonuclease TaqMan genotyping assays and polymerase chain reaction in a group of 165 patients who underwent coronary artery stenting. Basal and procedure coronary angiography were analyzed in search of angiographic predictors of restenosis and follow-up angiography was analyzed in search of binary restenosis. Patients with IL-1B-511 TT genotype had a 1.89-fold increased risk of developing restenosis. The analysis considering the lesions treated demonstrated that the lesions of patients with IL-1B-511 TT genotype had a 3.44-fold increased risk of developing restenosis. When the analysis considered the type of stent, the risk of developing restenosis was increased in lesions of patients with TT genotype (odds ratio = 4.50) who underwent coronary bare-metal stent implantation. Multiple logistic analysis identified IL-1B-511 TT genotype as an independent predictor for restenosis. The results suggest that IL-1B-511 polymorphism could be involved in the risk of developing restenosis after coronary stent placement.     

白细胞介素1B-511多态性与侵袭性牙周炎的关系

目的研究中国人群中IL-1B-511位点单核苷酸多态性(single nucleotide polymorphism,SNP)与侵袭性牙周炎(aggressive periodontitis,AgP)之间的关系.方法提取122名AgP患者和95名健康对照者外周静脉血基因组DNA,应用聚合酶链反应-限制性片段长度多态性的方法,分析IL-1B-511位点SNP与AgP的关联性.结果男性AgP组杂合基因型的频率较男性健康对照组升高并有统计学意义(P=0.048);A2 基因型/等位基因A2与吸烟联合作用显著增加了AgP的易感性(基因型:P=0.022;等位基因:P=0.006).结论IL-1B-511位点的SNP可能与中国人群中男性个体的AgP易感性有关;该位点的SNP与吸烟可能对AgP的易感性具有联合效应.     

白细胞介素1B基因启动子区-511位点C/T基因多态性与冠心病严重程度的相关性

目的探讨白细胞介素1B(interleukin1B,IL1B)基因启动子区-511位点C/T基因多态性与冠心病(coronary heart disease,CHD)严重程度的相关性。方法采用聚合酶链反应-限制性片段长度多态性分析的方法,检测127例CHD患者和152名对照组的IL1B-511位点C/T基因型;采用酶法测定血脂各项水平。结果IL1B-511位点C/T基因多态性在急性冠脉综合征(acute coronary syndrome,ACS)组和对照组间的分布差异存在统计学意义(χ2=5.72,P<0.01),CT及TT基因型患者患ACS的相对风险度约是CC基因型的2.56倍(比值比=2.56,95%可信区间=1.17~5.59);CHD组中,携带T等位基因的患者血清总胆固醇(6.09±0.97)mmol/L及低密度脂蛋白-胆固醇(3.97±0.92)mmol/L水平显著高于其他患者(5.12±0.56)mmol/L及(2.87±0.71)mmol/L(P<0.05)。结论IL1B-511位点C/T基因多态性与CHD的严重程度存在相关,其机理可能是该位点DNA变异影响了IL1B的分泌加重了炎症的反应及血脂紊乱。     

Étude des polymorphismes des gènes de l’interleukine-1 et de l’antagoniste du récepteur de l’interleukine-1 chez des patients atteints de polyarthrite rhumatoïde

Objectives

One of the most important pro-inflammatory cytokines in the pathophysiology of rheumatoid arthritis (RA) is interleukin 1 (IL-1). The purpose of this study is to evaluate the association between IL-1B (-511), IL-1 (+3953), IL-1 RN variable number of tandem repeat (VNTR) polymorphisms and the occurrence in Algerian patients with rheumatoid arthritis. We also analyze their correlations with clinical and biological phenotypes.

Patients and methods

One hundred and forty-seven patients with RA (119 women, 28 men) and 127 controls (70 women, 57 men) were included in the study. The analysis of two polymorphisms of IL-1B-511 and IL-1B+3953 was done by PCR-RFLP. Analysis of IL1-RN VNTR polymorphism was performed by PCR.

Results

No significant difference in genotype, allelic and haplotype distribution at the three polymorphisms was observed between RA patients and controls. However, the genotype (T/T) polymorphism of IL-1B-511 is more frequent in the group of patients with positive ACPA compared with negative ACPA group (Pc = 0.01, OR = 4.65). Moreover, we noted that the haplotype (IL-1RN* 1/IL-1B-511T/IL-1B+3953C) was more frequent (Pc = 0.03, OR = 2.05) in the positive ACPA group.

Conclusion

The association between the allele 1 of IL-1 RN VNTR, T allele of IL1B-511 and C allele of IL1-B +3953 polymorphisms seems to predispose to the synthesis of ACPA and therefore to the occurrence of ACPA positive RA. Further studies with a larger number of patients are needed to define the real role of IL-1 in the susceptibility to or severity of RA.     

Effect of IL-1β and TNF-α polymorphisms on the prognosis and survival of gastric cancer patients

So far, a number of association studies have focused on the effect of polymorphisms in IL-1β and TNF-α genes on the susceptibility to gastric cancer (GC). Here, we evaluate the possible association between common polymorphisms in the IL-1β and TNF-α genes with various clinicopathological characteristics, including overall survival of GC patients. Restriction fragment length polymorphism analysis was performed for IL-1β-31(T?>?C) and IL-1β-511(C?>?T) and TNF-α-857 (C?>?T) polymorphisms in 130 GC patients. IL-1β-31CC and IL-1β-511TT genotypes held a significantly lower risk of lymphatic invasion (IL-1β-31CC vs. others: adjusted OR?=?0.39, 95% CI?=?0.15-0.96, P?=?0.04, IL-1β-511TT vs. others: adjusted OR?=?0.23, 95% CI?=?0.08-0.67, P?=?0.007). The IL-1β-31CC and IL-1β-511TT genotypes were weakly associated with reduced risk of venous invasion (IL-1β-31CC vs. others: adjusted OR?=?0.35, 95% CI?=?0.12-1.05, P?=?0.06, IL-1β-511TT vs. others: adjusted OR?=?0.32, 95% CI?=?0.08-1.20, P?=?0.09). The IL-1β-511TT genotype was also weakly associated with reduced risk of lymph node metastasis (IL-1β-511TT vs. others: adjusted OR?=?0.42, 95% CI?=?0.17-1.04, P?=?0.06). When the TNF-α-857CT and TNF-α-857-TT genotypes were considered as T carrier, the patients with TNF-α-857T carrier showed significantly better overall survival than patients with CC genotype (P?=?0.011). GC patients who have both IL-1β-31 CC and IL-1β-511 TT genotypes and have at least one of protective genotypes (IL-1β-31 CC, IL-1β-511 TT, TNF-α-857 T carrier) were also associated with better prognostic factors, such as lymphatic and venous invasion better survival. IL-1β-31CC, IL-1β-511TT genotype, and TNF-α-857T carrier may have protective effect against GC progression.     

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     

Uterine Leiomyoma is Associated with a Polymorphism in the Interleukin 1-β Gene

Problem  To investigate whether polymorphisms in the interleukin-1β (IL-1β) gene are associated with uterine leiomyoma.
Method of study  Case–control study in a collective of 131 patients and 280 controls. Genotyping of the IL-1β-511 and IL-1β-3954 polymorphism was performed by PCR amplification and subsequent RFLP analysis.
Results  A significant difference in the allele frequencies of the IL-1β-511 C Conclusion  The IL-1β-511 promoter polymorphism is related to an increased susceptibility to uterine leiomyoma, suggesting that this polymorphism does contribute to the development of this disease.     

Genetic association of interleukin-1 haplotypes with gastritis and precancerous lesions in North Indians

Background We evaluated the association of functional variants of IL-1 genes with the development of gastritis and precancerous lesions, which are known to be influenced by inflammatory response against Helicobacter pylori. Methods After upper gastrointestinal (GI) endoscopy, 120 patients with gastritis were tested for H. pylori infection using rapid urease test, modified Giemsa staining and IgG anti-CagA ELISA. All patients and 243 healthy controls were genotyped for IL-1B (-511 C/T) and IL-IRN (VNTR) genes using PCR-RFLP/PCR. Results IL-1B (−511 C/T) genotype/allele were not associated with gastritis. IL-1RN 1/2 genotype carriers had susceptibility to gastritis (p = 0.025, OR = 1.7). Individuals with the IL-1RN 1/1 genotype (p = 0.05, OR = 0.65) and IL-1B −511*T-IL-1RN *1 haplotype were at low risk for gastritis (p = 0.043, OR = 0.72). High secretor haplotype combinations (C1-/T2+, C1-T1+ and T1+/T2+) did not influence neutrophilic infiltration, glandular atrophy or intestinal metaplasia. Conclusions We identified that individuals with the IL-1RN 1/2 genotype had increased risk for gastritis. IL-1B −511*T-IL-1RN *1 (T1) haplotype carriers were at decreased risk for gastritis and no significant association was observed for precancerous lesions in North Indians.