IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants' data from 21 studies

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Cornelia Huth, Iris M Heid, Caren Vollmert, Christian Gieger, Harald Grallert, Johanna K Wolford, Birgit Langer, Barbara Thorand, Norman Klopp, Yasmin H Hamid, Oluf Pedersen, Torben Hansen, Valeriya Lyssenko, Leif Groop, Christa Meisinger, Angela Döring, Hannelore Löwel, Wolfgang Lieb, Christian Hengstenberg, Wolfgang Rathmann & 25 others Stephan Martin, Jeffrey W Stephens, Helen Ireland, Hugh Mather, George J Miller, Heather M Stringham, Michael Boehnke, Jaakko Tuomilehto, Heiner Boeing, Matthias Möhlig, Joachim Spranger, Andreas Pfeiffer, Ingrid Wernstedt, Anders Niklason, Abel López-Bermejo, José-Manuel Fernández-Real, Robert L Hanson, Luis Gallart, Joan Vendrell, Anastasia Tsiavou, Erifili Hatziagelaki, Steve E Humphries, H-Erich Wichmann, Christian Herder, Thomas Illig

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20,000 participants from 21 published and unpublished studies.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.
Original languageEnglish
JournalDiabetes
Volume55
Issue number10
Pages (from-to)2915-21
Number of pages7
ISSN0012-1797
DOIs
Publication statusPublished - 2006

    Research areas

  • Case-Control Studies, Diabetes Mellitus, Type 2, Genetics, Population, Humans, Interleukin-6, Odds Ratio, Polymorphism, Genetic, Promoter Regions, Genetic, Risk

ID: 38336462