Variations of the interleukin-6 promoter are associated with features of the metabolic syndrome in Caucasian Danes.
OBJECTIVE
The cytokine interleukin 6 (IL-6) is an essential regulator of the acute phase response associated with insulin-resistant states including type 2 diabetes and obesity. Three polymorphisms at positions -597, -572, and -174 of the IL6 promoter have been reported to influence IL6 transcription. The aim of this study was to investigate whether the IL6 promoter polymorphisms were associated with features of the WHO-defined metabolic syndrome and related quantitative traits in 7,553 Caucasian Danes.


METHODS
Using analysis of PCR-generated primer extension products by mass spectrometry we examined -597 G/A, -572 G/C, and -174 G/C IL6 variants in the population-based Inter99 study cohort of middle-aged people (n=6,164) and in a group of type 2 diabetic patients (n=1,389).


RESULTS
The -174 G/C and -597 G/A polymorphisms were in strong linkage disequilibrium (R(2)=0.95). In the Inter99 cohort the -174 G-allele was associated with insulin resistance (p<0.02) and dyslipidaemia (p<0.007) whereas the C-allele of the -572 polymorphism was associated with increased serum insulin release during an OGTT (p<0.0005). Composite genotype or haplotype analyses of all 3 IL6 promoter variants showed associations with type 2 diabetes (p<0.002), obesity (p<0.02), and the metabolic syndrome (p<0.01).


CONCLUSIONS
The present studies suggest that single-nucleotide polymorphisms and composite genotypes or haplotypes of the IL6 promoter may be associated with several features of the metabolic syndrome in Caucasians.
Hamid
Y H
YH
Steno Diabetes Center, Niels Steensens Vej 2, 2820, Gentofte, Copenhagen, Denmark. yah@steno.dk
Rose
C S
CS
Urhammer
S A
SA
Glümer
C
C
Nolsøe
R
R
Kristiansen
O P
OP
Mandrup-Poulsen
T
T
Borch-Johnsen
K
K
Jorgensen
T
T
Hansen
T
T
Pedersen
O
O
D001483:Base Sequence; D015331:Cohort Studies; D017931:DNA Primers; D003718:Denmark; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D044465:White People / Q000235:genetics
D017931:DNA Primers; D015850:Interleukin-6