Dataset Information

Association between interleukin-21 gene rs6822844 polymorphism and rheumatoid arthritis susceptibility.

ABSTRACT: Controversial results concerning the association between a polymorphism rs6822844 in the interleukin (IL) 21 (IL-21) gene and rheumatoid arthritis (RA) have existed. A meta-analysis to confirm above relationships is necessary to be performed immediately. We conducted a search in the PubMed database, covering all papers published up to 20 October 2018. Overall, six case-control studies with 3244 cases and 3431 healthy controls were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of this association. Publication bias was assessed with both Egger's and Begg's tests. After calculation, we found that IL-21 rs6822844 polymorphism could decrease RA risk in overall genetic models (allelic contrast: OR = 0.77, 95% CI = 0.62-0.97, P=0.024; TG versus GG: OR = 0.68, 95% CI = 0.50-0.92, P=0.013, and dominant genetic model: OR = 0.72, 95% CI = 0.55-0.94, P=0.016). Similarly, stratified analysis by race, source of control, significantly decreased association was found in Asians, Caucasians and hospital-based (HB) control source. Finally, in the subgroup analysis of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) status, poorly decreased relationship was detected between IL-21 rs6822844 polymorphism and RF negative and ACPA positive RA risk, respectively. No obvious evidence of publication bias was detected in overall analysis. In summary, our study indicated that IL-21 rs6822844 polymorphism was significantly associated with decreased RA susceptibility.

SUBMITTER: Ren K

PROVIDER: S-EPMC6695501 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Association between interleukin-21 gene rs6822844 polymorphism and rheumatoid arthritis susceptibility.

Ren Kewei K Tang Jilei J Nong Luming L Shen Nan N Li Xiaolong X

Bioscience reports 20190815 8

Controversial results concerning the association between a polymorphism <i>rs6822844</i> in the interleukin (IL) 21 (IL-21) gene and rheumatoid arthritis (RA) have existed. A meta-analysis to confirm above relationships is necessary to be performed immediately. We conducted a search in the PubMed database, covering all papers published up to 20 October 2018. Overall, six case-control studies with 3244 cases and 3431 healthy controls were included. Odds ratios (ORs) and 95% confidence intervals ( ...[more]

PMID: 31366568

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Project description:BackgroundThe pathogenesis of rheumatoid arthritis (RA) is an immune imbalance, in which various inflammatory immune cells and pro-inflammatory factors are involved. Interleukin-17 (IL-17), a potent pro-inflammatory cytokine, has been found to have increased expression in the joints of patients with RA compared to healthy individuals. However, the causal relationship between the expression level of IL-17 or IL-17 receptor (IL-17R) and RA remained unknown. In this study, two-sample Mendelian randomization (MR) was used to investigate the causal relationship between IL-17 and RA.MethodsSummary statistics for RA (14,361 RA cases and 43,923 healthy controls) and IL-17 (3,301 samples) were obtained from an available meta-analysis of published genome-wide association studies (GWAS). Relevant single nucleotide polymorphisms (SNPs) were selected by executing quality control steps from the GWAS summary results. Then we used bi-directional two-sample Mendelian randomization (MR) and multi-variable MR (MVMR) analysis to examine evidence of causality. MR and MVMR analyses progressed mainly using inverse variance weighted (IVW), weighted median (WM), and MR-Egger regression methods, which were applied to the genetic instrumental variables (IVs) of IL-17A/IL-17 RA, IL-17C/IL-17 RC, and IL-17D/IL-17RD and RA. For assessing the robustness of the results, we also carried out a sensitivity analysis to assess heterogeneity and pleiotropy, such as MR-Egger, leave-one-out, and MR pleiotropy residual sum and outlier (MR-PRESSO).ResultsTwo-sample MR Analysis showed the causal relationship between IL-17A/IL-17RA and RA. The presence of genetically high IL-17A/IL-17RA may increase the risk of RA (IL-17A(OR = 1.095; 95% C.I., 0.990-1.210, p.adj = 0.013), IL-17RA(OR = 1.113, 95%CI = 1.006-1.231, p.adj = 0.006)). However, the results indicated that IL-17C/IL-17RC, and IL-17D/IL-17RD demonstrated no causal impact on RA (IL-17C(OR = 1.007, 95%CI = 0.890-1.139, p.adj = 0.152), IL-17RC(OR = 1.006, 95%CI = 0.904-1.119, p.adj = 0.152), IL-17D(OR = 0.979, 95%CI = 0.843-1.137, p.adj = 0.130), IL-17RD(OR = 0.983, 95%CI = 0.876-1.104, p.adj = 0.129)). Furthermore, MVMR analysis shown that IL-17RA(OR = 1.049, 95% CI: 0.997-1.102, p.adj = 0.014) was associated with increased risk of RA. Sensitivity analysis showed no heterogeneity and pleiotropy, suggesting that the above results were robust and reliable.ConclusionThe MR analysis provides evidence that IL-17A/IL-17RA are risk factors for RA. This emphasizes the importance of intervention on IL-17A/IL-17RA in patients with RA. Developing drugs that limit IL-17A may reduce the risk of RA.

Project description:ObjectivesRheumatoid arthritis is a chronic inflammatory autoimmune disease. This study aimed to determine the association of interleukin-17A-197G/A polymorphism with rheumatoid arthritis in Sudanese patients.MethodsA case-control study was conducted between March and December 2018. Clinical and demographic data of the study participants were collected and analyzed. Polymerase chain reaction restriction fragment length polymorphism molecular technique was done to investigate interleukin-17A-197G/A polymorphisms. All statistical tests were considered statistically significant when p < 0.05.ResultsThe study population included 266 participants aged between 1 and 85 years, with an average of 40 years, classified into 85 (31.2%) cases (mean age 48.5 ± 11.3 years), and 181 (68.8%) controls (mean age 35.3 ± 15.9 years). The interleukin-17A homozygote AA genotype was more frequent among the control group compared to the case group; 95 (52.5%) and 7 (8.2%), respectively. The homozygote GG and the heterozygote AG genotypes were proportionally not different among the cases and control groups; 13 (54.2%) and 11 (45.8%), and 65 (46.4%) and 75 (53.6%), respectively. According to the distribution of interleukin-17A genotypes, a statistically significant difference was observed among cases with the interleukin-17A AA and AG genotypes, p values 0.001 and 0.004, respectively. For the association interleukin-17A genotypes and family history a negatively significant association was reported (95% confidence interval, -0.219, p value = 0.001). There was also a negatively significant association of interleukin-17A genotypes and anti-cyclic citrullinated peptide (95% confidence interval, -0.141, p value = 0.002).ConclusionThis study is the first study in Sudan established the association between interleukin-17A-197G/A (rs2275913) polymorphisms and susceptibly to rheumatoid arthritis. These findings appeal for further research in Sudan to investigate the exact role of IL-17A in immunopathology and disease severity among Sudanese rheumatoid arthritis.

Project description:BACKGROUND:The single nucleotide polymorphisms of interleukin-21 (IL-21) gene were confirmed to be related to various diseases, but no studies have examined the possible role of IL-21 single nucleotide polymorphisms (SNPs) (rs907715, rs2221903, and rs12508721) in gastric precancerous lesions. AIM:To explore the associations between SNPs of IL-21 gene (rs907715, rs2221903, and rs12508721) and gastric precancerous lesions in a Chinese population. METHODS:Three SNPs of IL-21 were genotyped using polymerase chain reaction-ligase detection reaction in 588 cases and 290 healthy controls from May 2013 to December 2016 in northwestern China. Gastric precancerous lesions were confirmed by endoscopic examination and categorized as non-atrophic gastritis, atrophic gastritis, and intestinal metaplasia. Descriptive statistic and logistic regression were used for data analyses. RESULTS:IL-21 rs907715 genotype CC and C frequencies were higher in in patients with gastric precancerous lesions than in the controls (OR = 1.59, 95%CI: 1.06-2.38, P = 0.013; OR = 1.28, 95%CI: 1.01-2.22, P = 0.044, respectively) after adjusting for confounding factors. For SNP rs907715 in intestinal metaplasia patients, significant differences between cases and controls were observed in the frequencies of genotype CC and C (OR = 1.92, 95%CI: 1.24-2.98, P = 0.004; OR = 1.53, 95%CI: 1.04-2.24, P = 0.028, respectively); for non-atrophic gastritis and atrophic gastritis patients, the CC and C genotypes showed no significant association with risk in all models. No association between either rs2221903 or rs12508721 and gastric precancerous lesions was found in the present study. In the haplotype analysis, the TC haplotype (rs907715 and rs12508721) and TT haplotype (rs2221903 and rs907715) were more frequent in the case group than control group (P < 0.05). CONCLUSION:Our findings indicate that SNP rs907715 of IL-21 gene is associated with gastric precancerous lesions. The TC haplotype (rs907715 and rs12508721) and TT haplotype (rs2221903 and rs907715) increased the risk of gastric precancerous lesions. If confirmed, these findings will shed light on the etiology of precancerous lesions.

Dataset Information

Association between interleukin-21 gene rs6822844 polymorphism and rheumatoid arthritis susceptibility.

Publications

Association between interleukin-21 gene rs6822844 polymorphism and rheumatoid arthritis susceptibility.

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