title: Comprehensive review of genetic association studies and meta-analysis on miRNA polymorphisms and rheumatoid arthritis and systemic lupus erythematosus susceptibility.
abstract: BACKGROUND
  MicroRNAs (miRNAs), small RNA molecules, play a role in the development and differentiation of immune cells in both innate and adaptive immune responses. Our study was aimed to investigate the association between three miRNA polymorphism and rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) by using meta-analysis approach.
  
  
  METHODS
  A PubMed database search was conducted during August 2013 to identify case-control studies of miRNAs and RA or SLE risk. Two authors independently extracted information on the study design, the characteristics of the study participants, exposure and outcome assessments. The fix-effects and random-effects models were used for the risk estimates by Stata 11.0 software.
  
  
  RESULTS
  Our meta-analysis of six case-control studies involving a total of 998 RA cases and 1493 controls identified no significant association between mir-146a rs2910164 and RA, with an overall OR of 0.843 (95% CI=0.642-1.105; CC vs. GG). No association was observed in three studies with a total of 1532 cases and 2168 controls between miR-146a rs2910164 and SLE risk (OR=0.911, 95% CI=0.710-1.171; CC vs. GG). Three studies with a total of 529 cases and 595 controls evaluated the mir-499 rs3746444 polymorphism and its association with RA. There was a decreased overall risk of RA under the allelic and genotypic models [OR=0.616, 95% CI=0.384-0.981, (T vs. C allele) and OR=0.386, 95% CI=0.226-0.659, (TT vs. CC)]. Two studies with 4826 cases and 4181 controls evaluated miR-146a rs57095329 and its association with SLE. There was a significant association between miR-146a rs57095329 and SLE (OR=1.263, 95% CI=1.136-1.405, G vs. A allele).
  
  
  CONCLUSIONS
  The present meta-analysis suggests important roles for the mir-499 rs3746444 polymorphism in RA, especially in the Caucasian population and for miR-146a rs57095329 polymorphism in SLE. Further studies with large sample size are needed to confirm these associations.
authors.affiliation: Department of Clinical Epidemiology and Evidence-based Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, China. Electronic address: fulingyucmu@sina.com.cn.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Internal Medicine, Shenjing Hospital, China Medical University, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Medical Informatics, China Medical University, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Clinical Epidemiology and Evidence-based Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Jingpu
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Clinical Epidemiology and Evidence-based Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Clinical Epidemiology and Evidence-based Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Clinical Epidemiology and Evidence-based Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wu
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C542542:MIRN146 microRNA, human; C548683:MIRN499 microRNA, human; D035683:MicroRNAs
keywords: Meta-analysis; MicroRNAs; Polymorphism; Rheumatoid arthritis; Systemic lupus erythematosus