Meta-Analysis of Associations of IL1 Receptor Antagonist and Estrogen Receptor Gene Polymorphisms with Systemic Lupus Erythematosus Susceptibility

<div><p>Systemic lupus erythematosus (SLE) is an autoimmune disease that affects a number of different organs and tissues. Interleukin-1 (IL1) and estrogen are considered potential elements in the pathology of SLE. Recently, the variable number of tandem repeats (VNTR) polymorphism in the IL1 receptor antagonist gene (<i>IL1-RN</i>) and <i>Pvu</i>II (rs2234693) and <i>Xba</i>I (rs9340799) polymorphisms in the estrogen receptor 1 gene (<i>ESR1</i>) have been associated with a predisposition to SLE. However, the evidence for these associations is inconclusive. We therefore conducted a meta-analysis to validate the roles of these polymorphisms in SLE susceptibility. We searched four databases and identified a total of 17 eligible articles comprising 24 studies. The Newcastle-Ottawa quality assessment scale was used to assess the qualities of the selected studies. We assessed the strengths of the associations using odds ratios (ORs) with 95% confidence intervals (95% CIs). Regarding the <i>IL-1RN</i> VNTR, the 2 allele significantly increased SLE susceptibility (2 vs. L: OR = 1.34, 95% CI = 1.03–1.73, <i>P</i> = 0.03). The <i>ESR1 Pvu</i>II CC/CT genotype was also associated with SLE susceptibility (CC/CT vs. TT: OR = 1.25, 95% CI = 1.06–1.47, <i>P</i> = 0.01), and the difference was especially pronounced among Asians (CC/CT vs. TT: OR = 1.33, 95% CI = 1.04–1.69, <i>P</i> = 0.02). No significant association between the <i>ESR1 Xba</i>I polymorphism and SLE susceptibility was observed in the overall analysis. However, a marginally significant association between the GG/GA genotype was found in individuals of Asian descent (GG/GA vs. AA: OR = 1.30, 95% CI = 1.01–1.67, <i>P</i> = 0.04). These results indicate that the <i>IL1-RN</i> VNTR 2 allele, <i>ESR1 Pvu</i>II CC/CT genotype and <i>ESR1 Xba</i>I GG/GA genotype may increase SLE susceptibility, especially in Asian individuals.</p>