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.

A study of the association between plasma interleukin-21 gene polymorphism and the susceptibility to rheumatoid arthritis in Egyptian patients

“…A study conducted on a cohort of Iraqi individuals discovered that the GG genotype/G allele of IL-21 (rs2055979) may be related to a tendency to multiple sclerosis (15) . In our results, there was no significant association as regards ESR, CRP, and RF with IL-21 genotypes in the RA group, similar to another study (7) that found; the analysis of ESR, CRP and RF with the IL-21 and IL-21R polymorphisms did not show differences between the variant genotypes.…”

“…In the pathogenesis of RA, inflammatory cytokines play an important role in inducing the inflammatory response and releasing other inflammatory mediators (11) . One of these cytokines is IL-21, which has various effects on the immune system and plays an essential role in the proliferation of B cells, differentiation of plasma cells, and immunoglobulin synthesis; therefore, the effects of IL-21 on B cells may take part in the development of different autoimmune disorders (7,8) . In recent years, IL-21 has played a vital role in the pathogenesis and progression of RA (12) .…”

“…The IL-21 receptor (IL-21R) is abundantly expressed on CD4+ T cells, dendritic cells, macrophages, and synovial fibroblasts. These immune cells sense IL-21 in the micro-environment and do a series of complicated actions (7) . IL-21 has a range of immune impacts and plays a vital role in the proliferation of B-cells, differentiation of plasma cells, and immunoglobulin synthesis; hence, IL-21's actions on B cells may have a role in the development of various autoimmune disorders (8) .…”

Association between interleukin-1 alpha rs1800587 polymorphism and rheumatoid arthritis: A meta-analysis

“…Therefore, these variables must be examined in subsequent articles, regardless of the difficulties in assessing environmental exposures and study design. 22,23 Some limitations exist in our meta-analysis. To begin with, we only enrolled researches in Chinese and English, thus, some potentially eligible researches published in other languages might be omitted.…”

“…Therefore, these variables must be examined in subsequent articles, regardless of the difficulties in assessing environmental exposures and study design. 22 , 23 …”