IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants' data from 21 studies.
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20,000 participants from 21 published and unpublished studies.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.
Huth
Cornelia
C
GSF-Institute of Epidemiology, Neuherberg, Germany.
Heid
Iris M
IM
Vollmert
Caren
C
Gieger
Christian
C
Grallert
Harald
H
Wolford
Johanna K
JK
Langer
Birgit
B
Thorand
Barbara
B
Klopp
Norman
N
Hamid
Yasmin H
YH
Pedersen
Oluf
O
Hansen
Torben
T
Lyssenko
Valeriya
V
Groop
Leif
L
Meisinger
Christa
C
Döring
Angela
A
Löwel
Hannelore
H
Lieb
Wolfgang
W
Hengstenberg
Christian
C
Rathmann
Wolfgang
W
Martin
Stephan
S
Stephens
Jeffrey W
JW
Ireland
Helen
H
Mather
Hugh
H
Miller
George J
GJ
Stringham
Heather M
HM
Boehnke
Michael
M
Tuomilehto
Jaakko
J
Boeing
Heiner
H
Möhlig
Matthias
M
Spranger
Joachim
J
Pfeiffer
Andreas
A
Wernstedt
Ingrid
I
Niklason
Anders
A
López-Bermejo
Abel
A
Fernández-Real
José-Manuel
JM
Hanson
Robert L
RL
Gallart
Luis
L
Vendrell
Joan
J
Tsiavou
Anastasia
A
Hatziagelaki
Erifili
E
Humphries
Steve E
SE
Wichmann
H-Erich
HE
Herder
Christian
C
Illig
Thomas
T
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
D015850:Interleukin-6