title: Association between polymorphism of interleukin-1 beta and interleukin-1 receptor antagonist gene and asthma risk: a meta-analysis.
abstract: BACKGROUND
  Asthma is a complex polygenic disease in which gene-environment interactions are important. A number of studies have investigated the polymorphism of IL-1β -511C/T and IL-1RA genes in relation to asthma susceptibility in different populations. However, the results of individual studies have been inconsistent. Accordingly, we conducted a comprehensive meta-analysis to investigate the association between the IL-1β -511C/T and IL-1RA polymorphism and asthma risk.
  
  
  METHODS
  Data were collected from the following electronic databases: Pub Med, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), ISI Web of Knowledge, and Google Scholar Search databases with the last report up to July 2013. Finally, 15 studies were included in our meta-analysis. We summarized the data on the association between IL-1β -511C/T and IL-1RA polymorphism and risk of asthma in the overall population and performed subgroup analyses by ethnicity, mean of age, and source of controls. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the associations between IL-1β -511C/T and IL-1RA polymorphism and asthma risk. Statistical analysis was performed with Review Manager 5.1.
  
  
  RESULTS
  A total of 15 case-control studies were included in the meta-analysis of IL-1β -511C/T (1,385 cases and 1,964 controls) and IL-1RA (2,800 cases and 6,359 controls) genotypes. No association was found between IL-1β -511C/T polymorphism and asthma risk (dominant model: OR = 1.11, 95% CI: 0.99-1.25, P = 0.07, P Heterogeneity = 0.06; recessive model: OR = 1.04, 95% CI: 0.91-1.20, P = 0.55, P Heterogeneity = 0.11). Subgroup analysis based on ethnicity (Asian and Caucasian), source of controls (population-based controls and hospital-based controls), and mean of age (adulthood and childhood) did not present any significant association. The overall results showed that the IL-1RA polymorphism was related to an increased risk of asthma (homozygote model: OR = 1.32, 95% CI: 1.12-1.56, P = 0.0009, P Heterogeneity = 0.87; recessive model: OR = 1.39, 95% CI: 1.18-1.63, P = 0.0001, P Heterogeneity = 0.82). Similar results were found in the subgroup analyses by ethnicity, mean of age, and source of controls. Sensitivity analysis did not perturb the results.
  
  
  CONCLUSIONS
  This meta-analysis provided strong evidence that the IL-1RA polymorphism was a risk factor of asthma, especially in Caucasian populations. However, no association was found for IL-1β -511C/T genotype carriers. Larger scale studies are needed for confirmation.
authors.affiliation: Department of Respiratory Diseases, Tongji Hospital, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
authors.forename: Yuanzhou
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Respiratory Diseases, Tongji Hospital, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Respiratory Diseases, Tongji Hospital, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
authors.forename: Weining
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Department of Respiratory Diseases, Tongji Hospital, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Respiratory Diseases, Tongji Hospital, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
mesh_terms: D044466:Asian People / Q000235:genetics; D001249:Asthma / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta
references.citation: J Biol Chem. 2011 Sep 23;286(38):32883-9
references.pmid: 21799018
references.citation: J Clin Invest. 1997 Jan 1;99(1):117-24
references.pmid: 9011565
references.citation: Cytokine. 2013 Jun;62(3):389-94
references.pmid: 23602199
references.citation: Eur J Immunol. 2003 Apr;33(4):991-1000
references.pmid: 12672065
references.citation: Allergy. 2003 May;58(5):393-6
references.pmid: 12752325
references.citation: J Clin Lab Anal. 2003;17(5):168-73
references.pmid: 12938145
references.citation: J Interferon Cytokine Res. 2004 Apr;24(4):253-60
references.pmid: 15144571
references.citation: Am J Respir Cell Mol Biol. 2004 Jun;30(6):830-6
references.pmid: 14754758
references.citation: Lancet. 1989 Jun 24;1(8652):1432-5
references.pmid: 2567438
references.citation: Eur J Pharmacol. 1992 Mar 31;213(3):331-6
references.pmid: 1377630
references.citation: N Engl J Med. 1993 Jan 14;328(2):106-13
references.pmid: 8439348
references.citation: Biometrics. 1994 Dec;50(4):1088-101
references.pmid: 7786990
references.citation: J Allergy Clin Immunol. 1995 Jun;95(6):1236-45
references.pmid: 7797792
references.citation: Allergy. 2006 Feb;61(2):239-44
references.pmid: 16409203
references.citation: Med J Aust. 2006 Mar 6;184(5):226-9
references.pmid: 16515433
references.citation: Eur Respir J. 2007 Mar;29(3):502-8
references.pmid: 17107994
references.citation: Arch Dis Child. 2007 Nov;92(11):1032-5
references.pmid: 17954484
references.citation: Allergy Asthma Proc. 2008 Sep-Oct;29(5):468-74
references.pmid: 18926055
references.citation: Indian J Pediatr. 2008 Oct;75(10):1019-23
references.pmid: 18810365
references.citation: Clin Exp Immunol. 2009 Jan;155(1):21-7
references.pmid: 19076825
references.citation: J Clin Immunol. 2009 Jan;29(1):57-62
references.pmid: 18763028
references.citation: Curr Opin Genet Dev. 2009 Jun;19(3):279-82
references.pmid: 19481925
references.citation: Respir Res. 2010;11:23
references.pmid: 20181264
references.citation: J Allergy Clin Immunol. 2010 Nov;126(5):926-38
references.pmid: 20926125
references.citation: Carcinogenesis. 2011 Apr;32(4):522-9
references.pmid: 21252117
references.citation: Thorax. 1997 May;52(5):407-10
references.pmid: 9176529
references.citation: Lancet. 1997 Aug 2;350(9074):326-9
references.pmid: 9251637
references.citation: Int Rev Immunol. 1998;16(5-6):457-99
references.pmid: 9646173
references.citation: Am J Respir Crit Care Med. 1999 Feb;159(2):487-94
references.pmid: 9927362
references.citation: Arthritis Rheum. 1999 Jun;42(6):1093-100
references.pmid: 10366101
references.citation: Thorax. 1999 Sep;54(9):825-57
references.pmid: 10456976
references.citation: Respir Res. 2005;6:52
references.pmid: 15935090
references.citation: Cytokine. 2000 Jun;12(6):819-21
references.pmid: 10843772
references.citation: Biochem Biophys Res Commun. 2000 Sep 24;276(2):607-12
references.pmid: 11027520
references.citation: Curr Opin Pediatr. 2001 Jun;13(3):267-77
references.pmid: 11389363
references.citation: J Allergy Clin Immunol. 2002 Mar;109(3):514-6
references.pmid: 11898000
references.citation: Int Immunol. 2003 Apr;15(4):483-90
references.pmid: 12663678
references.citation: PLoS One. 2011;6(12):e27627
references.pmid: 22205926