Abstract
BackgroundThe biological mechanisms driving disease chronicity in rheumatoid arthritis (RA) are largely unidentified. Therefore, we aimed to determine genetic risk factors for RA.MethodsIn this case–control study, which includes samples from 499 patients and 507 healthy controls, six single‐nucleotide polymorphisms (SNPs) in interleukin‐2 receptor subunit alpha (IL2RA) and IL2RB were selected. Genotyping was performed using the Agena MassARRAY platform, and the statistical analyses were performed using the chi‐squared and Fisher's exact tests, genetic model analysis, and haplotype analysis.ResultIn the allele model, using the chi‐squared test, the result showed that rs791588 in IL2RA was associated with a decreased RA risk (odds ratios [OR] = 0.74, 95% confidence intervals [CI] = 0.62–0.89, p = 0.0014) after adjusting for age and gender. In the genetic model, logistic regression analyses revealed that rs791588 was associated with a decreased risk of RA under the codominant model, dominant model, recessive model, and log‐additive model. Stratification analysis revealed that two SNPs (rs791588 and rs2281089) were significantly associated with a reduced RA risk in an allele and genetic model after stratification by gender or age (p < 0.05). In addition, the haplotypes “Crs12569923Grs791588” and “Crs12569923Trs791588” of IL2RA was associated with an increased risk of RA adjusted by age and gender (OR = 1.35, 95% CI: 1.12–1.64, p = 0.0016; OR = 1.24, 95% CI: 1.03–1.48, p = 0.021).ConclusionThis finding indicates that the inherited altered genetic constitution at IL2RA may predispose to a less destructive course of RA.
Highlights
Rheumatoid arthritis (RA), one of the most common systemic autoimmune disorders, is characterized by peripheral synovial joint inflammation, which leads to long‐ term joint damage, loss of function, a poor quality of life, and increases mortality (Silman & Pearson, 2002)
The “G/T‐G/G” genotype of rs791588 in interleukin‐2 receptor subunit alpha (IL2RA) plays a protective role to reduce rheumatoid arthritis (RA) risk as revealed by the dominant model when compared to the “T/T” genotype (OR = 0.77, 95% confidence intervals (CI) = 0.60 –0.99, p = 0.046)
We discovered that rs791588 (IL2RA) and rs2281089 (IL2RB) significantly decreased the risk of RA in females and people aged under 54
Summary
Rheumatoid arthritis (RA), one of the most common systemic autoimmune disorders, is characterized by peripheral synovial joint inflammation, which leads to long‐ term joint damage, loss of function, a poor quality of life, and increases mortality (Silman & Pearson, 2002). Advances in genotyping technology and the use of single‐ nucleotide polymorphism (SNP) assays have facilitated the application of whole genome association approaches to link genetic variants with disease susceptibility (Bowes & Barton, 2008; Criswell et al, 2006). Heritability studies have revealed a critical role of genetic susceptibility in the progression of joint destruction in RA; the heritability is estimated as 45%– 58% (Adeline et al, 2014). Large genome‐wide association studies (GWAS) have identified more than 30 loci involved in RA pathogenesis (De, 2011). Little studies have investigated the association between genetic variants in IL2RA and IL2RB and the risk of RA. We performed a case– control study to analyze the associations between IL2RA and IL2RB and the risk of RA
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