Interleukin-6 Rs1800795 Research Articles

The association of genetic polymorphisms with cerebral palsy: a meta-analysis

The aim of our meta-analysis was to summarize quantitatively the association of genetic polymorphisms with cerebral palsy (CP). We identified 16 studies on the association of genetic polymorphisms with CP in Pubmed, Elsevier Science Direct, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, and Wanfang. Eleven of these studies (involving a total of 2533 cases and 4432 controls) were used in the current meta-analysis. A study was included if (1) it was published up to September 2010 and (2) it was a case-control study. We excluded one study of family members because the analysis was based on linkage considerations. Meta odds ratios and 95% confidence intervals based on fixed-effects models or random-effects models were dependent on Cochran's Q statistic. We examined the relationship between alleles, as well as genotypes and susceptibility to CP. Meta-analysis was performed for 17 genetic polymorphisms: apolipoprotein E (ε2,ε3,ε4), methylenetetrahydrofolate reductase (MTHFR) (rs1801133), coagulation factor II (rs1799963]), coagulation factor V (rs6025), coagulation factor VII (rs5742910/rs6046), interleukin-6 (IL-6) (rs1800795), endothelial nitric oxide (rs1800779/rs1799983/rs3918226), fibrinogen β-polypeptide (rs1800790), plasminogen activator inhibitor 1 (rs1799768/rs7242), TNF-β lymphotoxin α precursor (rs1041981), adducin 1 (α) (rs4961), ADRB2 (rs1042714), and tumour necrosis factor α (rs1800629). We found a significant association between CP and IL-6 (rs1800795) [C vs G: odds ratio (OR) 1.79, 95% confidence interval (CI) 1.44-2.22, p<0.001; CC+GC vs GG: OR 1.72, 95% CI 1.29-2.29, p=0.002; CC vs GG+GC: OR 2.17, 95% CI 1.52-3.09, p<0.001], but no other genetic polymorphisms. This meta-analysis demonstrated that CP is associated with the genetic polymorphism IL-6 (rs1800795).

Lack of association of IL-10 gene polymorphisms with prostate cancer: Evidence from 11,581 subjects

Published data on the association between interleukin-10 (IL-10) gene polymorphisms and prostate cancer (PCa) are inconclusive. To derive a more precise estimation of the association, we conducted a meta-analysis. Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Excerpta Medica Database and Chinese Biomedical Literature Database, with the last report up to September 2010. The odds ratio (OR) and its 95% confidence interval (95%CI) were used to assess the strength of association. A total of 13 separate studies including 5503 cases and 6078 controls based on the search criteria were involved in this meta-analysis. Meta-analysis was performed for three IL-10 gene polymorphisms (rs1800896, rs1800871, and rs1800872). We found no association between IL-10 gene rs1800896 polymorphism and PCa in overall population (G versus A: OR = 1.00, 95%CI = 0.91–1.10, P = 0.99; AG + GG versus AA: OR = 1.18, 95%CI = 0.97–1.43, P = 0.10; GG versus AA + AG: OR = 1.04, 95%CI = 0.86–1.26, P = 0.67). In subgroup analysis, similar results were found in Caucasian (G versus A: OR = 0.99, 95%CI = 0.84–1.18, P = 0.92; AG + GG versus AA: OR = 1.32, 95%CI = 0.90–1.94, P = 0.16; GG versus AA + AG: OR = 1.07, 95%CI = 0.89–1.28, P = 0.48), and Asian (G versus A: OR = 0.97, 95%CI = 0.78–1.20, P = 0.78; AG + GG versus AA: OR = 1.07, 95%CI = 0.79–1.45, P = 0.65; GG versus AA + AG: OR = 1.24, 95%CI = 0.38–4.07, P = 0.73) populations. We did not detect an association between IL-10 gene rs1800871 polymorphism and PCa in overall population (T versus C: OR = 0.96, 95%CI = 0.85–1.08, P = 0.51; CT + TT versus CC: OR = 0.94, 95%CI = 0.80–1.11, P = 0.48; TT versus CC + CT: OR = 0.94, 95%CI = 0.81–1.10, P = 0.44). Similar results were found in Asian population (T versus C: OR = 0.85, 95%CI = 0.71–1.09, P = 0.09; CT + TT versus CC: OR = 0.72, 95%CI = 0.52–1.17, P = 0.05; TT versus CC + CT: OR = 0.89, 95%CI = 0.68–1.17, P = 0.39). We found no association between IL-10 gene rs1800872 polymorphism and PCa in overall population (A versus C: OR=1.03, 95%CI = 0.96–1.11, P = 0.41; CA + AA versus CC: OR = 1.04, 95%CI = 0.92–1.17, P = 0.56; AA versus CC + CA: OR = 1.02, 95%CI = 0.85–1.22, P = 0.87). Similar results were found in Caucasian population (A versus C: OR = 1.06, 95%CI = 0.98–1.16, P = 0.16; CA + AA versus CC: OR = 1.07, 95%CI = 0.85–1.35, P = 0.57; AA versus CC + CA: OR = 1.23, 95%CI = 0.92–1.64, P = 0.17). This meta-analysis suggests that there is no association between IL-10 gene rs1800896, rs1800871 and rs1800872 polymorphisms and PCa.

Inflammatory Gene Variants in the Tsimane, an Indigenous Bolivian Population with a High Infectious Load

The Tsimane of lowland Bolivia are an indigenous forager-farmer population living under conditions resembling pre-industrial European populations, with high infectious morbidity, high infection and inflammation, and shortened life expectancy. Analysis of 917 persons ages 5 to 60+ showed that allele frequencies of 9 SNPs examined in the apolipoprotein E (apoE), C-reactive protein (CRP), and interleukin-6 (IL-6) genes differed from some European, African, and north Asian-derived populations. The apoE2 allele was absent, whereas four SNPs related to CRP and IL-6 were monomorphic: CRP (rs1800947, rs3093061, and rs3093062) and IL-6 (rs1800795). No significant differences in apoE, CRP, and IL-6 variants across age were found CRP levels were higher in carriers of two CRP proinflammatory SNPs, whereas they were lower in carriers of apoE4. Taken together, the evidence for (1) different allele frequencies between the Tsimane and other populations and (2) the correlations of CRP and apoE alleles with blood CRP may suggest that these variants are under selection in response to a high infection environment.

Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary disease

Asthma and chronic obstructive pulmonary disease (COPD) are chronic respiratory diseases involving an interaction between genetic and environmental factors. Interleukin-13 (IL13) has been suggested to have a role in both asthma and COPD. We investigated whether single nucleotide polymorphisms (SNPs) in the IL13 pathway may contribute to the susceptibility and severity of asthma and COPD in adults. Twelve SNPs in IL13 pathway genes -IL4, IL13, IL4RA, IL13RA1, IL13RA2 and STAT6- were genotyped in subjects with asthma (n = 299) and in subjects with COPD or healthy smokers (n = 992). Genetic association was evaluated using genotype and allele models for asthma severity, atopy phenotypes and COPD susceptibility. Linear regression was used to determine the effects of polymorphism on baseline lung function (FEV(1), FEV(1)/FVC). In asthmatics, three IL13 SNPs - rs1881457(-1512), rs1800925(-1111) and rs20541(R130Q) - were associated with atopy risk. One SNP in IL4RA1 [rs1805010(I75V)] was associated with asthma severity, and several IL13 SNPs showed borderline significance. IL13 SNPs rs1881457(-1512) and rs1800925(-1111) were associated with better FEV(1) and FEV(1)/FVC in asthmatics. IL13 SNPs rs2066960(intron 1), rs20541(R130Q) and rs1295685(exon 4) were associated with COPD risk and lower baseline lung function in the recessive model. In females, but not in males, rs2250747 of the IL13RA1 gene was associated with COPD and lower FEV(1). These data suggest that IL13 SNPs (promoter and coding region) and, to a lesser extent, IL4RA SNPs may contribute to atopy and asthma. We also provide tentative evidence that IL13 SNPs in the coding region may be of significance in COPD susceptibility.

Interleukin-6 (IL-6) and receptor (IL6-R) gene haplotypes associate with amniotic fluid protein concentrations in preterm birth

Spontaneous preterm birth (PTB-gestational age <37 weeks) occurs in approximately 450 000 births annually in the United States and is one of the leading causes of neonatal morbidity and mortality. Risk of PTB is affected by complex gene-environment interactions that are not well understood. We examined the PTB candidate gene, Interleukin 6 (IL-6) and its receptor (IL6-R) in both Caucasian (145 PTB and 194 term maternal; 140 PTB and 179 term fetal) and African-American (76 PTB and 191 term maternal; 66 PTB and 183 term fetal) DNA. Eight single nucleotide polymorphisms (SNPs) in IL-6 and 22 SNPs in IL6R were examined for association with IL-6 amniotic fluid (AF) concentrations, as concentration of IL-6 is a hypothesized risk factor. In addition, IL-6 and IL6-R SNPs were analyzed for associations with PTB. Haplotype associations were tested by sliding windows. No strong single marker effects were observed in Caucasians; however, in African-American maternal IL-6R marker rs4553185 associated with PTB (allele P = 4.49 x 10(-3) and genotype P = 0.01). The strongest haplotype associations were observed in IL-6R with IL-6 cytokine concentration as outcome: Caucasian fetal (rs4601580-rs4845618) P = 1.6 x 10(-3) and African-American maternal (rs4601580-rs4845618-rs6687726-rs7549338) P = 2.30 x 10(-3). Significant results converged on three regions in the two genes: in IL-6 markers rs1800797, rs1800796 and rs1800795; in IL-6R markers rs4075015, rs4601580, rs4645618, rs6687726 and rs7549338 and markers rs4845623, rs4537545 and rs4845625. In conclusion, our results suggest that IL-6 AF concentration, in situations of PTB, result from variation in IL-6 and more importantly IL-6R.

Modifying Effects of IL‐6 Polymorphisms on Body Size–Associated Breast Cancer Risk

The association between obesity and breast cancer risk is complex. We examined whether the association between body size and breast cancer risk is modified by interleukin-6 (IL6) genotype. Five polymorphisms in the IL-6 gene (rs1800797/-596A>G, rs1800796/-572G>C, rs1800795/-174G>C, rs2069832/IVS2G>A, and rs2069849 exon 5 C>T) were studied. We investigated IL6 genotypes and haplotypes with indicators of body size among non-Hispanic white (NHW) and Hispanic/American Indian (AI) breast cancer cases and controls living in the Southwestern United States. We observed lower mean levels of BMI among NHW women who carried one or two copies of the GGCAC haplotype (in order: rs1800797, rs1800796, rs1800795, rs2069832, and rs2069849; P trend 0.02). This haplotype, with an estimated frequency of 43% in NHW study controls, was considerably less common in Hispanic/AI controls (19%). We did not detect significant interactions between IL6 genotypes or haplotypes and BMI categorized as low/normal (<25), overweight (25 to <30), or obese (> or =30) and breast cancer risk in either NHW or Hispanic/AI women. However, we detected consistent and significant interactions between waist-to-hip ratio (WHR) and IL6 rs1800795/-174 G>C genotype for breast cancer risk. These associations were restricted to postmenopausal NHW women. Among women without recent hormone exposure, those with a WHR >0.9 and the rs1800795 GG genotype had a greater than threefold increased risk of breast cancer (odds ratios (ORs) 3.22, 95% confidence intervals (CIs) 1.27, 817) when compared with women with a WHR <0.8 and the rs1800795 GG genotype (P interaction 0.01). These data suggest that IL-6 genotypes may influence breast cancer risk in conjunction with central adiposity.

The interleukin-10 gene promoter polymorphism −1087AG does not correlate with clinical outcome in non-Hodgkin's lymphoma

The Interleukin 10 (IL-10) gene is highly polymorphic, and the IL-10(-1087AG) (rs1800896) gene variation is the only so far studied intensively in association with certain diseases. Conflicting data have been published about an association of IL-10(-1087AG) gene variation with lower rates of complete remission and lower overall survival (OS) in patients with diffuse large B-cell lymphoma. To further investigate this in malignant lymphoma, we established the IL-10 genotypes in patients from the NHL-B1/ B2 studies from the German High-Grade Non-Hodgkin's Lymphoma Study Group. In our study, allele frequencies of lymphoma patients are comparable as in healthy controls. No increase of IL-10(-1087G) alleles was found. In addition we did not find any difference in OS or event-free survival between patients with IL-10(-1087AA) and the other genotypes. Comparable results were obtained for the IL-10 loci at -3538 (A/T), -1354 (A/G), -824 (C/T) and -597 (A/C) (rs1800890, rs1800893, rs1800871 and rs1800872).