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

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; 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

doi:10.2337/db06-0600

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

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 RathmannStephan 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

79 Citations (Scopus)

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20,000 participants from 21 published and unpublished studies.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.

Original language	English
Journal	Diabetes
Volume	55
Issue number	10
Pages (from-to)	2915-21
Number of pages	7
ISSN	0012-1797
DOIs	https://doi.org/10.2337/db06-0600
Publication status	Published - 2006

Keywords

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

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10.2337/db06-0600

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Huth, C., Heid, I. M., Vollmert, C., Gieger, C., Grallert, H., Wolford, J. K., Langer, B., Thorand, B., Klopp, N., Hamid, Y. H., Pedersen, O., Hansen, T., Lyssenko, V., Groop, L., Meisinger, C., Döring, A., Löwel, H., Lieb, W., Hengstenberg, C., ... Illig, T. (2006). IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants' data from 21 studies. Diabetes, 55(10), 2915-21. https://doi.org/10.2337/db06-0600

Huth, C, Heid, IM, Vollmert, C, Gieger, C, Grallert, H, Wolford, JK, Langer, B, Thorand, B, Klopp, N, Hamid, YH, Pedersen, O , Hansen, T, Lyssenko, V, Groop, L, Meisinger, C, Döring, A, Löwel, H, Lieb, W, Hengstenberg, C, Rathmann, W, Martin, S, Stephens, JW, Ireland, H, Mather, H, Miller, GJ, Stringham, HM, Boehnke, M, Tuomilehto, J, Boeing, H, Möhlig, M, Spranger, J, Pfeiffer, A, Wernstedt, I, Niklason, A, López-Bermejo, A, Fernández-Real, J-M, Hanson, RL, Gallart, L, Vendrell, J, Tsiavou, A, Hatziagelaki, E, Humphries, SE, Wichmann, H-E, Herder, C & Illig, T 2006, 'IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants' data from 21 studies', Diabetes, vol. 55, no. 10, pp. 2915-21. https://doi.org/10.2337/db06-0600

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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.",

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

author = "Cornelia Huth and Heid, {Iris M} and Caren Vollmert and Christian Gieger and Harald Grallert and Wolford, {Johanna K} and Birgit Langer and Barbara Thorand and Norman Klopp and Hamid, {Yasmin H} and Oluf Pedersen and Torben Hansen and Valeriya Lyssenko and Leif Groop and Christa Meisinger and Angela D{\"o}ring and Hannelore L{\"o}wel and Wolfgang Lieb and Christian Hengstenberg and Wolfgang Rathmann and Stephan Martin and Stephens, {Jeffrey W} and Helen Ireland and Hugh Mather and Miller, {George J} and Stringham, {Heather M} and Michael Boehnke and Jaakko Tuomilehto and Heiner Boeing and Matthias M{\"o}hlig and Joachim Spranger and Andreas Pfeiffer and Ingrid Wernstedt and Anders Niklason and Abel L{\'o}pez-Bermejo and Jos{\'e}-Manuel Fern{\'a}ndez-Real and Hanson, {Robert L} and Luis Gallart and Joan Vendrell and Anastasia Tsiavou and Erifili Hatziagelaki and Humphries, {Steve E} and H-Erich Wichmann and Christian Herder and Thomas Illig",

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T1 - IL6 gene promoter polymorphisms and type 2 diabetes

T2 - joint analysis of individual participants' data from 21 studies

AU - Huth, Cornelia

AU - Heid, Iris M

AU - Vollmert, Caren

AU - Gieger, Christian

AU - Grallert, Harald

AU - Wolford, Johanna K

AU - Langer, Birgit

AU - Thorand, Barbara

AU - Klopp, Norman

AU - Hamid, Yasmin H

AU - Pedersen, Oluf

AU - Hansen, Torben

AU - Lyssenko, Valeriya

AU - Groop, Leif

AU - Meisinger, Christa

AU - Döring, Angela

AU - Löwel, Hannelore

AU - Lieb, Wolfgang

AU - Hengstenberg, Christian

AU - Rathmann, Wolfgang

AU - Martin, Stephan

AU - Stephens, Jeffrey W

AU - Ireland, Helen

AU - Mather, Hugh

AU - Miller, George J

AU - Stringham, Heather M

AU - Boehnke, Michael

AU - Tuomilehto, Jaakko

AU - Boeing, Heiner

AU - Möhlig, Matthias

AU - Spranger, Joachim

AU - Pfeiffer, Andreas

AU - Wernstedt, Ingrid

AU - Niklason, Anders

AU - López-Bermejo, Abel

AU - Fernández-Real, José-Manuel

AU - Hanson, Robert L

AU - Gallart, Luis

AU - Vendrell, Joan

AU - Tsiavou, Anastasia

AU - Hatziagelaki, Erifili

AU - Humphries, Steve E

AU - Wichmann, H-Erich

AU - Herder, Christian

AU - Illig, Thomas

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

KW - Case-Control Studies

KW - Diabetes Mellitus, Type 2

KW - Genetics, Population

KW - Humans

KW - Interleukin-6

KW - Odds Ratio

KW - Polymorphism, Genetic

KW - Promoter Regions, Genetic

KW - Risk

U2 - 10.2337/db06-0600

DO - 10.2337/db06-0600

M3 - Journal article

C2 - 17003362

SN - 0012-1797

VL - 55

SP - 2915

EP - 2921

JO - Diabetes

JF - Diabetes

IS - 10

ER -

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

Abstract

Keywords

UN SDGs

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