Association of IL-1β and IL-6 gene polymorphisms with recurrent spontaneous abortion in a Chinese Han population

As certain cytokines may play a role in unexplained recurrent spontaneous abortion (RSA) and also some cytokine gene polymorphisms may affect the level of cytokine production, the aim of this study was to investigate the relationship between Chinese RSA and polymorphisms of the genes coding for interleukin (IL)-1β (-31C/T, -511C/T, +3954C/T) and IL-6 (-634C/G). Women (n = 162) with at least three consecutive spontaneous abortions and 156 ethnically matched healthy women with at least one successful pregnancy were included. Genotypes were determined using restriction fragment length polymorphism analysis of polymerase chain reaction products. No significant differences were found in the IL-1β-31T, -511T and +3954T distributions between the RSA group and the control group. On the other hand, the frequencies of the IL-6-634GG genotype and -634G allele were significantly decreased in the RSA group versus the control group (genotype: P = 0.0003; allele: P = 0.002), suggesting the IL-6-634C/G polymorphism might be a possible genetic protective factor for RSA.     

Single nucleotide polymorphisms in intron 2 of the human interleukin-1 receptor antagonist (IL-1Ra) gene: further definition of the IL-1 beta and IL-1Ra polymorphisms in North American Caucasians and Taiwanese Chinese

Previous studies have suggested that a variable number tandem repeat (VNTR) polymorphism in the second intron of the interleukin-1 receptor antagonist (IL-1Ra) gene and the single nucleotide polymorphisms at positions -511 and +3954 of the IL-1beta gene might be associated with increased risks of chronic inflammatory diseases, autoimmune diseases and gastric cancer. In the present study, IL-1beta and IL-1Ra genotypes were analyzed among Asians in Taiwan and Caucasians in North America. We identified a novel polymorphism with 3 nucleotide substitutions in the IL-1Ra VNTR 2-repeat allele. One of the substitutions corresponds with the fourth 3' end nucleotide of the reverse primer that is often used for analysis of the IL-1Ra-associated VNTR locus. Mismatching between this primer and the 2-repeat allele can cause misleading amplification results when stringent conditions are used for annealing. The estimated haplotype frequencies of the variant IL-1 genes were significantly different between Taiwanese and Caucasians. The frequency of the pro-inflammatory IL-1Ra 2-repeat allele was significantly lower in Taiwanese than in Caucasians. In contrast, the frequencies of the pro-inflammatory IL-1beta -511T allele and +3954C allele were significantly higher among Taiwanese compared with Caucasians.     

Single nucleotide polymorphism of interleukin-1β associated with Helicobacter pylori infection in immune thrombocytopenic purpura

To examine the role of genetic factors in development of immune thrombocytopenic purpura (ITP) in association with Helicobacter pylori infection, gene polymorphisms within the loci for human leukocyte antigen class II, interleukin (IL)-1β (−511), tumor necrosis factor-β (+252), immunoglobulin (Ig)G1 heavy chain (+643), and Igκ light chain (+573) were determined in 164 adults with ITP and 75 healthy controls. Of these gene polymorphisms, the IL-1β (−511) T allele was less frequently detected in H.   pylori -infected than in H.   pylori -uninfected (58% vs 81%, P  = 0.01, odds ratio = 0.31) ITP patients diagnosed before age 50. These findings suggest that a single nucleotide polymorphism within the IL-1β (−511) may affect susceptibility to early-onset ITP associated with H.   pylori infection.     

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-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.     

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.     

Asthma and atopy are associated with chromosome 17q21 markers in Chinese children

Background:  Single-nucleotide polymorphism (SNP)-based genome-wide association study revealed that markers on chromosome 17q21 were linked to childhood asthma but not atopy in Caucasians, with the strongest signal being detected for the SNP rs7216389 in the ORMDL3 gene. Such association was unknown in Chinese. This study delineated the allele and genotype frequencies of 10 SNPs at chromosome 17q21, and investigated the relationship between these SNPs and asthma and plasma IgE in southern Chinese children.
Methods:  Asthmatic children and non-allergic controls were recruited from pediatric clinics. Their plasma total and aeroallergen-specific IgE concentrations were measured by immunoassay. Ten SNPs on 17q21 region were genotyped by multiplex SNaPshot™, and their genotype associations with asthma traits analyzed using multivariate regression.
Results:  315 patients and 192 controls were enrolled. The allele frequency for C allele of rs7216389 varied significantly from 0.232 in our controls, 0.389 in Han Chinese to 0.536 in Caucasians. Asthma diagnosis was associated with rs11650680 and five other SNPs including rs7216389 ( P  =   0.019–0.034), whereas atopy was associated only with rs11650680 ( P  =   0.0004). Linear regression revealed the covariates for plasma total IgE to be significant for rs11650680 ( P  =   0.008–0.0002). Haplotypic associations were found with atopy and increased plasma total IgE, with the respective odds ratios and 95% confidence intervals for TTTCCGTT haplotype to be 0.21 and 0.09–0.52 ( P  =   0.0002) and 0.41 and 0.18–0.90 ( P  =   0.025).
Conclusion:  Childhood asthma and atopy are associated with chromosome 17q21 in Chinese, but such association may involve genes other than ORMDL3 in this region.     

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     

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.     

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.     

Production of TNF-α and IL-1β by Peripheral Blood Mononuclear Cells in Carriers of Different Allele Variants of the Gene

Associations of cytokine production by mononuclear cells and the TNF-α genetic polymorphism in positions -238, -308, -376, -857, -1031, and of IL-1β in positions -31 and +3954 were studied. The data on distribution of allele and genotype incidence and on the level of spontaneous and mitogen-induced production of these cytokines by donor mononuclear cells demonstrated a statistically significant association of TNF-α production by mononuclear cells with polymorphic variants of the gene promoter regions -238 > A (rs361525) and -857C > T (rs1799724). Carriers of -238GG/-308GG/-857CC/-1031NC genotype were characterized by low production of TNF-α, while carriers of -31TT/+3954CT genotype were characterized by low IL-1β stimulation index in response to mitogen in comparison with carriers of other genotype combinations.     

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.     

中国广西人白细胞介素-21基因rs2221903 T/C遗传多态性研究

目的:了解白细胞介素-21(IL-21)基因单核苷酸多态性(SNP)各等位基因及基因型在中国广西地区人群中的分布频率,比较其在不同种族间分布的差异。方法:采用单碱基延伸的PCR技术和DNA测序法检测199例中国广西人的IL-21基因rs2221903 T/C多态性,并结合人类基因组计划(Hapmap)公布的欧洲人、非洲人、日本人和中国北京人的SNP分型数据,比较分析广西人与其他种族人群的基因型及等位基因分布频率的差异。结果:广西人IL-21基因型TT、TC和CC频率分别为75.38%、23.62%和1.01%;等位基因T、C频率分别为87.19%和12.81%。其基因型频率在男女组间比较差异无统计学意义(P>0.05)。广西人与欧洲和非洲人群比较,IL-21基因多态性分布频率差异均有统计学意义(P<0.05);而与日本人和中国北京人比较差异无统计学意义(P>0.05)。结论:在中国广西人群中存在IL-21基因多态性,且与其他种族人群比较存在显著性差异,这种差异对于人类学的研究可能起重要的作用。     

Epistatic effect of C-reactive protein (CRP) single nucleotide polymorphism (SNP) +1059 and interleukin-1B SNP +3954 on CRP concentration in healthy male blood donors

Baseline C-reactive protein (CRP) concentrations are indicative of persons prone to cardiovascular diseases and are about 40-50% heritable. We have previously shown that interleukin (IL)-1B +3954 allele T is associated with lower CRP concentration. In this study, we aimed to examine the effect of this polymorphism together with the CRP +1059 gene polymorphism on baseline CRP concentrations, and genotyped 336 healthy blood donors for CRP +1059 (G-->C) and IL-1B +3954 (C-->T) polymorphisms. In men, the carriers of the CRP +1059 C-allele had significantly lower CRP values than GG homozygotes (0.66 versus 0.43 mg l(-1), up to -35%, P = 0.009). No significant difference was found in women. When the data were stratified for both of these polymorphisms in men, CRP +1059 GG homozygotes had low CRP concentrations only if they were allele-T carriers of IL-1B +3954 simultaneously (0.93 versus 0.50 mg l(-1), P = 0.013). Genotype CRP +1059 GG/IL-1B +3954 CC was associated with an almost 3-fold risk of a higher baseline CRP value [odds ratio (OR) 2.84 (CI 1.03-6.07)]. Thus, both IL-1B +3954 (C-->T) and CRP +1059 (G-->C) polymorphisms influence baseline CRP values and act independently of each other in male subjects. These polymorphisms might be predictive markers of persons prone to cardiovascular diseases.     

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。     

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.     

Association of polymorphic variants of IL-1β and IL-1RN genes in the development of Graves’ disease in Kashmiri population (North India)

Purpose

Graves’ disease (GD) is a multigenic, organ specific autoimmune disorder with a strong genetic predisposition and IL-1β has been shown to be involved in its pathogenesis. The present study was aimed to determine the genetic associations between polymorphisms of IL-1β gene promoter region (?511?T>C) (rs16944), exon 5 (+3954 C>T) (rs1143634) and IL-1RN gene VNTR (rs2234663) polymorphism in patients with GD in ethnic Kashmiri population.

The CD226 gene in susceptibility of type 1 diabetes

The rs763361 single nucleotide polymorphism (SNP) within the CD226 gene has recently been reported as a novel susceptible locus for type 1 diabetes. The CD226 gene is implicated in the regulation of a number of cells involved in immune mechanisms leading to β-cell destruction in type 1 diabetes. The aim of the present study was to confirm the association of the CD226 gene with type 1 diabetes in Estonian population. The TT genotype [odds ratio (OR) = 2.29, 95% confidence interval (CI) = 1.25–4.18, P  = 0.0071) and the T allele (OR = 1.48, 95% CI = 1.11–1.98, P  = 0.0084) of the rs763361 SNP were associated with the risk of type 1 diabetes. The current study replicates the novel association of the rs763361 SNP in susceptibility of type 1 diabetes and supports the CD226 gene as a susceptible candidate locus for type 1 diabetes outside the major histocompatibility complex region.     

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.