title: Meta-analysis of associations of IL1 receptor antagonist and estrogen receptor gene polymorphisms with systemic lupus erythematosus susceptibility.
abstract: 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 (IL1-RN) and PvuII (rs2234693) and XbaI (rs9340799) polymorphisms in the estrogen receptor 1 gene (ESR1) 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 IL-1RN VNTR, the 2 allele significantly increased SLE susceptibility (2 vs. L: OR = 1.34, 95% CI = 1.03-1.73, P = 0.03). The ESR1 PvuII CC/CT genotype was also associated with SLE susceptibility (CC/CT vs. TT: OR = 1.25, 95% CI = 1.06-1.47, P = 0.01), and the difference was especially pronounced among Asians (CC/CT vs. TT: OR = 1.33, 95% CI = 1.04-1.69, P = 0.02). No significant association between the ESR1 XbaI 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, P = 0.04). These results indicate that the IL1-RN VNTR 2 allele, ESR1 PvuII CC/CT genotype and ESR1 XbaI GG/GA genotype may increase SLE susceptibility, especially in Asian individuals.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Jiangning District, Nanjing, Jiangsu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical College of Nanjing University, Gulou District, Nanjing, Jiangsu, China.
authors.forename: Jin-wei
authors.initials: JW
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Jiangning District, Nanjing, Jiangsu, China.
authors.forename: Xing-xin
authors.initials: XX
authors.lastname: Xue
authors.affiliation: Department of Nosocomial Infection Control, General Hospital of Beijing Military Region, Dongcheng District, Beijing, China.
authors.forename: Zhi-gang
authors.initials: ZG
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Jiangning District, Nanjing, Jiangsu, China.
authors.forename: Jia-jia
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Jiangning District, Nanjing, Jiangsu, China.
authors.forename: Shai-di
authors.initials: SD
authors.lastname: Tang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Jiangning District, Nanjing, Jiangsu, China.
authors.forename: Shao-wen
authors.initials: SW
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Jiangning District, Nanjing, Jiangsu, China; Department of General Practice, Kangda College, Nanjing Medical University, Jiangning District, Nanjing, Jiangsu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Jiangning District, Nanjing, Jiangsu, China; Institute of Epidemiology and Microbiology, Huadong Research Institute for Medicine and Biotechnics, Nanjing, Jiangsu, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Nosocomial Infection Control, General Hospital of Beijing Military Region, Dongcheng District, Beijing, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Xia
mesh_terms: D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D011110:Polymorphism, Genetic; D011960:Receptors, Estrogen / Q000235:genetics*
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D011960:Receptors, Estrogen