title: IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants' data from 21 studies.
abstract: Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, -174G>C (rs1800795) and -573G>C (rs1800796), have been investigated for association with type 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on >20,000 participants from 21 published and unpublished studies. Collected data represent eight different countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 -174G>C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found between IL6 -573G>C and type 2 diabetes. The observed association of the IL6 -174 C-allele with a reduced risk of type 2 diabetes provides further evidence for the hypothesis that immune mediators are causally related to type 2 diabetes; however, because the association is borderline significant, additional data are still needed to confirm this finding.
authors.affiliation: GSF-Institute of Epidemiology, Neuherberg, Germany.
authors.forename: Cornelia
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authors.lastname: Wolford
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authors.lastname: Stringham
authors.forename: Michael
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authors.lastname: Boehnke
authors.forename: Jaakko
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authors.lastname: Tuomilehto
authors.forename: Heiner
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authors.lastname: Boeing
authors.forename: Matthias
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authors.lastname: Möhlig
authors.forename: Joachim
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authors.lastname: Pfeiffer
authors.forename: Ingrid
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authors.lastname: Wernstedt
authors.forename: Anders
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authors.lastname: Niklason
authors.forename: Abel
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authors.lastname: López-Bermejo
authors.forename: José-Manuel
authors.initials: JM
authors.lastname: Fernández-Real
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hanson
authors.forename: Luis
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authors.lastname: Gallart
authors.forename: Joan
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authors.lastname: Vendrell
authors.forename: Anastasia
authors.initials: A
authors.lastname: Tsiavou
authors.forename: Erifili
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authors.lastname: Hatziagelaki
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
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authors.lastname: Illig
mesh_terms: D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005828:Genetics, Population; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012306:Risk
chemical_list: D015850:Interleukin-6