title: Association between Interleukin-6 (G174C and G572C) promoter gene polymorphisms and risk of ischaemic stroke: A meta-analysis.
abstract: BACKGROUND
  Interleukin-6 (IL-6), as one of the most typical pro-inflammatory and immunoregulatory cytokines, is believed to be associated with the genesis and maintenance of inflammatory response. Genetic association studies (GAS) that have investigated the association between Interleukin 6 (G174C and G572C) promoter gene polymorphisms and susceptibility to ischemic stroke (IS) which have produced contradictory and unconvincing results.
  
  
  OBJECTIVE
  The aim of this meta-analysis is to provide a relatively comprehensive account of the association of IL-6 (G174C and G572C) polymorphisms with susceptibility to IS.
  
  
  METHODS
  A literature search was conducted using electronic database PubMed, Medline, and Trip database for all case-control studies investigating for association of IL-6 genetic polymorphisms with ischemic stroke published till August 30, 2014. The following combinations of main keywords were used: ('Interleukin-6' or 'IL-6') and ('ischaemic stroke or 'cerebral infarction' or 'IS') and ('genetic polymorphism' or 'single nucleotide polymorphisms' or 'SNP'). Pooled Odds ratios (ORs) and 95% confidence intervals (CIs) were determined for IL-6 gene-disease association. Meta-analysis was carried out using Revman 5.3 software.
  
  
  RESULTS
  16 case-control studies involving a total of 3,317 IS patients and 3,432 healthy controls for G174C polymorphism and 3 case-control studies with a total of 2,001 IS patients and 2,027 healthy controls for G572C IL-6 gene polymorphisms were included in a meta-analysis. For IL-6 G174C gene polymorphisms, no significant association was observed under dominant [GC + CC vs. GG: OR = 1.01, 95% CI: 0.77-1.34, P = 0. 92], recessive [CC vs. GG + GC: OR = 0.82, 95% CI: 0.40-1.70, P = 0. 59] and allelic model [C vs. G Allele: OR = 0.99, 95% CI: 0.74-1.31, P = 0. 93]. For IL-6 G572C, no significant association was observed under dominant [CC vs. GG + GC: OR = 0.99, 95% CI: 0.57-1.71, P = 0. 97], recessive [CC vs. GG + GC: OR = 0.93, 95% CI: 0.60-1.45, P = 0. 75] and allelic model [C vs. G Allele: OR = 0.95, 95% CI: 0.66-1.36, P = 0. 76].
  
  
  CONCLUSIONS
  This meta-analysis shows that IL-6 (G174C) and IL-6 (G572C) gene polymorphisms may not be associated with an increased susceptibility to IS. Further studies are required for confirmatory results.
authors.affiliation: Department of Neurology, All India Institute of Medical Sciences, New Delhi, INDIA.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Department of Neurology, All India Institute of Medical Sciences, New Delhi, INDIA.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Yadav
authors.affiliation: Department of Neurology, All India Institute of Medical Sciences, New Delhi, INDIA.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Neurology, All India Institute of Medical Sciences, New Delhi, INDIA.
authors.forename: Ram
authors.initials: R
authors.lastname: Sagar
authors.affiliation: Department of Neurology, All India Institute of Medical Sciences, New Delhi, INDIA.
authors.forename: Awadh K
authors.initials: AK
authors.lastname: Pandit
authors.affiliation: Department of Neurology, All India Institute of Medical Sciences, New Delhi, INDIA.
authors.forename: Kameshwar
authors.initials: K
authors.lastname: Prasad
keywords: Cytokine; Inflammatory gene; Interleukin-6; Ischaemic stroke; Meta-analysis; Single nucleotide Polymorphisms