慢性乙型肝炎患者白细胞介素1受体拮抗剂基因多态性分析

目的 :探讨白细胞介素 1受体拮抗剂 (IL 1ra)基因多态性与慢性乙型肝炎的关系。方法 :应用聚合酶链反应技术对 199例慢性乙型肝炎患者和 2 49例正常人的白细胞介素 1受体拮抗剂基因 (IL 1RN)数目可变的串联重复多态性进行分析。结果 :IL 1ra基因的 5种不同组合等位基因 ,本研究只发现Ⅰ /Ⅰ、Ⅰ /Ⅱ、Ⅱ /Ⅱ和Ⅰ /Ⅳ 4种基因型 ,其中IL 1RNI等位基因频率在慢性乙型肝炎患者和正常人分别为 94.5 %和 90 .4% ,IL 1RNⅡ等位基因频率分别为 4.8%和 8.8%。慢性乙型肝炎患者和正常人IL 1RNⅠ /Ⅰ、Ⅰ /Ⅱ、Ⅱ /Ⅱ和Ⅰ /Ⅳ 4种基因型频率分别为 89.5 %和 81.1% ,8.5 %和 16.9% ,0 .5 %和 0 .4% ,1.5 %和 1.6%。慢性乙型肝炎组IL 1RNⅠ /Ⅱ基因型和IL 1RNⅡ等位基因频率明显低于正常对照组 (P <0 .0 5 )。结论 :IL 1RNⅡ等位基因影响慢性乙型肝炎易感性 ,但与慢性乙型肝炎HBVDNA复制无关     

慢性乙型肝炎患者白细胞介素-1受体拮抗剂IL-1ra基因多态性

目的探讨白细胞介素-1受体拮抗剂内含子2可变串联重复序列基因多态性与慢性乙型肝炎相关性.方法利用聚合酶链式反应技术对56例慢性乙型肝炎及100例正常对照者的白细胞介素-1受体拮抗剂基因进行扩增.结果慢性乙型肝炎患者IL-1ra基因频率:IL1RN1/1 0.8214,IL1RN1/2 0.1607,IL1RN1/4 0.0179,IL-1ra等位基因频率:IL1RN*1 0.9107,IL1RN*2 0.0804,IL1RN*4 0.0089,与正常对照组无明显差异(p>0.05).结论慢性乙型肝炎患者IL-1ra基因多态性的分布与正常人无明显差异.     

慢性乙型肝炎患者白细胞介素-1受体拮抗剂IL-1ra基因多态性

目的 探讨白细胞介素-1受体拮抗剂内含子2可变串联重复序列基因多态性与慢性乙型肝炎相关性．方法 利用聚合酶链式反应技术对56例慢性乙型肝炎及100例正常对照者的白细胞介素-1受体拮抗剂基因进行扩增．结果 慢性乙型肝炎患者IL-1ra基因频率：IL1RN1／10．8214，IL1RN1／20．1607，IL1RN1／40．0179，IL-1ra等位基因频率：IL1RN ＊ 10．9107，IL1RN ＊ 20．0804，IL1RN ＊ 40．0089，与正常对照组无明显差异（p〉0．05）．结论 慢性乙型肝炎患者IL-1ra基因多态性的分布与正常人无明显差异．     

白细胞介素-1受体拮抗剂内含子2可变串联重复序列基因多态性与冠心病

目的　探讨白细胞介素 - 1受体拮抗剂内含子 2可变串联重复序列基因多态性与冠心病相关性 .方法　利用聚合酶链式反应技术对 86例冠心病及 10 0例正常对照者的白细胞介素 - 1受体拮抗剂基因进行扩增 .结果　冠心病患者IL - 1ra基因频率 :IL1RN1/ 10 .82 5 6 ,IL1RN1/ 2 0 .16 2 8,IL1RN1/ 30 .0 116 ,IL - 1ra等位基因频率 :IL1RN 10 .912 7,IL1RN 2 0 .0 814 ,IL1RN 30 .0 0 5 9,与对照组无差异 (p >0 .0 5 ) .结论　冠心病患者IL - 1ra基因多态性的分布与正常人无明显相关性     

白细胞介素-1受体拮抗剂基因多态性与变态性鼻炎相关性探讨

目的　探讨白细胞介素 - 1受体拮抗剂 (IL -lra)基因多态性与变态性鼻炎相关性 .方法　利用聚合酶链式反应技术对 6 9例变态性鼻炎患者及 15 6例正常对照者的IL -lra基因进行扩增 .结果　变态性鼻炎患者IL - 1ra基因频率 :IL1RN1/ 10 .8116 ,IL1RN1/ 2 0 .1739,IL1RN1/ 30 .0 14 5 ,IL - 1ra等位基因频率 :,IL1RN 10 .90 5 8,IL1RN 20 .0 86 9,IL1RN 30 .0 0 72 ,与对照组无差异 (p >0 .0 5 ) .结论　IL - 1ra基因多态性的分布与变态性鼻炎无明显相关性     

白细胞介素-1受体拮抗剂内含子2可变串联重复序列基因多态性与冠心病

目的探讨白细胞介素-1受体拮抗剂内含子2可变串联重复序列基因多态性与冠心病相关性.方法利用聚合酶链式反应技术对86例冠心病及100例正常对照者的白细胞介素-1受体拮抗剂基因进行扩增.结果冠心病患者IL-1ra基因频率:IL1RN1/1 0.8256,IL1RN1/2 0.1628,IL1RN1/3 0.0116,IL-1ra等位基因频率:IL1RN*1 0.9127,IL1RN*2 0.0814 ,IL1RN*3 0.0059 ,与对照组无差异(p>0.05).结论冠心病患者IL-1ra基因多态性的分布与正常人无明显相关性.     

广东汉族人儿童白细胞介素-1受体拮抗剂基因多态性

目的了解广东汉族人白细胞介素-1受体拮抗剂基因的分布特点.方法应用聚合酶链反应技术对156例正常人白细胞介素-1受体拮抗剂基因进行扩增并进行图谱分析.并进行了不同种族间的分析比较.结果广东汉族人群中IL-1ra基因表型频率:IL1RN1/1 0.8205,IL1RN1/2 0.1731,IL1RN1/3 0.0064,IL-1ra等位基因频率:IL1RN*1 0.9103,IL1RN*2 0.0865,IL1RN*3 0.0032.结论白细胞介素-1受体拮抗剂基因多态性在不同种族间分布存在着明显的差异.     

白细胞介素-1受体拮抗剂基因多态性与变态性鼻炎相关性探讨

目的探讨白细胞介素-1受体拮抗剂(IL-lra)基因多态性与变态性鼻炎相关性.方法利用聚合酶链式反应技术对69例变态性鼻炎患者及156例正常对照者的IL-lra基因进行扩增.结果变态性鼻炎患者IL-1ra基因频率:IL1RN1/1 0.8116,IL1RN1/2 0.1739,IL1RN1/3 0.0145,IL-1ra等位基因频率:,IL1RN*1 0.9058,IL1RN*2 0.0869,IL1RN*3 0.0072,与对照组无差异(p>0.05).结论 IL-1ra基因多态性的分布与变态性鼻炎无明显相关性.     

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.     

载脂蛋白E、白细胞介素-1α基因多态性与成都地区阿尔茨海默病的关联分析

目的　探讨载脂蛋白E(apolipoprotein E,APOE)和白细胞介素 - 1α(interleukin- 1α,IL- 1α)基因多态性与成都地区阿尔茨海默病 (Alzheimer's disease,AD)的关系。方法　用聚合酶链反应 -限制性片段长度多态性技术检测成都地区流行病学调查中诊断为 AD的 114例患者和 113名健康老年人 APOE基因和 IL - 1α基因多态性。结果　中度、重度 AD组含 APOEε4基因型频率 (2 8.6 % )显著高于轻度 AD组 (18.5 % )和正常对照组 (14 .2 % ) ,其中中度、重度 AD组与正常对照组差异有显著性 (OR=2 .4 ,95 % CI:1.1～5 .5 )。将ε4等位基因频率与ε2和ε3等位基因频率之和比较 ,中度、重度 AD组与正常对照组的差异有显著性 (OR=2 .6 ,95 % CI:1.3～ 5 .3)。 AD患者组和正常对照组 IL - 1α基因型和等位基因频率分布相似 ,差异无显著性 (P>0 .0 5 )。结论　 APOEε4等位基因与中、重度 AD相关联 ,是中、重度 AD的易感因素。 IL - 1α基因多态性与中国成都地区 AD患者无关联。     

Functional correlates of the interleukin-1 receptor antagonist gene polymorphism in the colonic mucosa in ulcerative colitis

Association studies have identified the interleukin-1 receptor antagonist gene allele 2(IL-1RN*2) as a marker of susceptibility in ulcerative colitis (UC). This study investigated the significance of the IL-1RN genotype with respect to protein and mRNA expression in the colonic mucosa. Homogenates of rectal biopsies from 99 UC and 54 controls were assayed for cytokines IL-1ra, IL-1a and IL-1b using ELISA. IL1RN, IL1A and IL1B genotypes were determined using restriction-enzyme analysis. The ability of the two IL1RN alleles to generate steady-state mRNA accumulation was assessed in the colonic mucosa of seven heterozygous patients. Stepwise linear regression demonstrated that IL-1RN genotype (P=0.001), diagnosis (P<0.0001) and treatment (P<0.03) were independent factors associated with the IL-1ra protein level whilst IL1RN genotype (P=0.005) and macroscopic inflammatory grade (P<0.0001) were associated with the IL-1ra/ total IL-1 ratio. The IL1RN*2 correlated with reduced IL-1ra and IL-1ra/IL-1 ratio with a gene dosage effect. In heterozygous UC patients the ratio of allele 1 mRNA / allele 2 steady state mRNA was always greater than 1 (range: 1.2-3.1) (P=0.018). The IL-1RN*2 is associated with reduced levels of IL-1ra protein and IL-1RN mRNA in the colonic mucosa, providing a biologically plausible explanation for the observed association of the allele with the disease.     

汉族人白细胞介素-18基因启动子多态性与慢性乙型肝炎的相关性研究

目的 探讨中国汉族人白细胞介素-18（interleukin-18,IL-18）基因启动子单核苷酸多态性及其与慢性乙型肝炎易感性之间的关系。方法 应用序列特异性引物一聚合酶链反应技术，检测231例慢性乙型肝炎患者和300名正常人儿．馏基因启动子-607C/A、-137G／C单核苷酸多态性位点基因型。结果 正常对照组和慢性乙型肝炎组中，IL-18基因启动子-607C/A位点3种基因型频率分别为CC型：0．22（66／300）和0．27（62／231），CA型：0．53（160／300）和0．50（116／231），AA型：0．25（74／300）和0．23（53／231）；IL-18基因启动子-137G／C位点3种基因型频率分别为GG型：0．67（202／300）和0．79（182／231），GC型：0．30（90／300）和0．19（45／231），CC型：0．03（8／300）和0．02（4／231）。经Y0检验，慢性乙型肝炎组IL-18基因启动子-137GG分布频率显著高于正常对照组（X^2=8．55，P=0．003），而-607C／-137C和-607A／-137C单倍型频率显著低于正常对照组。进一步比较慢性乙型肝炎患者儿．馏基因启动子多态性与乙型肝炎病毒（hepatitis Bvirus，HBV）DNA复制的关系，发现高水平HBV—DNA组-607位点AA基因型分布频率明显低于低水平HBV—DNA组（Y2=6．03，P=0．014）。结论 汉族人慢性乙型肝炎与IL-18基因启动子-607C/A、-137G／C单核苷酸多态性相关，其中IL-18基因启动子-137位点C等位基因可能对机体HBV感染有保护作用，而启动子-607位点AA型对感染后HBV—DNA的复制可能有抑制作用。     

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.     

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.     

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 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).     

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.     

Interleukin-1 receptor antagonist gene polymorphism,vaginal interleukin-1 receptor antagonist concentrations,and vaginal ureaplasma urealyticum colonization in pregnant women

Ureaplasma urealyticum is the microorganism most frequently isolated from amniotic fluids of women in preterm labor. The relationship between vaginal colonization with U. urealyticum, vaginal interleukin-1 receptor antagonist (IL-1ra) levels, and the IL-1ra genotype in pregnant women was examined. Vaginal specimens, obtained with a cotton swab from 207 women in their first trimester of pregnancy, were tested for IL-1ra concentrations by enzyme-linked immunosorbent assay and for U. urealyticum and IL-1ra genotypes by PCR. U. urealyticum was detected in 85 (41.1%) women. The median IL-1ra level was 450 ng/ml in women positive for U. urealyticum, as opposed to 225 ng/ml in women negative for this microorganism (P < 0.0001). Sixty-two percent of the 16 women who were homozygous for allele 2 of the IL-1ra gene (IL-1RN*2) were colonized with U. urealyticum, as opposed to 47% of the 49 women who were IL-1RN*1/IL-1RN*2 heterozygotes and 34% of the 133 women who were IL-1RN*1 homozygotes (P < 0.05). Median IL-1ra levels were 750 ng/ml in IL-1RN*2 homozygotes, 300 ng/ml in IL-1RN*1/IL-1RN*2 heterozygotes, and 250 ng/ml in IL-1RN*1 homozygotes (P = 0.02). The vast majority of subjects had an uneventful pregnancy and delivered a healthy infant at term. The IL-1ra genotype or U. urealyticum colonization was unrelated to birth weight. Pregnant women who are colonized with U. urealyticum during the first trimester have elevated vaginal IL-1ra concentrations and a higher prevalence of the IL-1RN*2 homozygote genotype than do noncolonized women.