A common polymorphism in the interleukin-6 gene promoter is associated with overweight.
OBJECTIVE
Human body fat mass is to a large extent genetically determined, but little is known about the susceptibility genes for common obesity. Interleukin-6 (IL-6) suppresses body fat mass in rodents, and IL-6 treatment increases energy expenditure in both rodents and humans. The -174 G/C single-nucleotide polymorphism (SNP) in the IL-6 gene promoter is common in many populations, and -174 C-containing promoters have been found to be weaker enhancers of transcription. Moreover, a SNP at position -572 in the IL-6 promoter has recently been reported to affect transcription. The objective was to investigate the association between the IL-6 gene promoter SNPs and obesity.


METHODS
Trans-sectional association study of IL-6 gene promoter SNPs and indices of obesity.


METHODS
Two study populations, the larger one consisting of hypertensive individuals (mean age 57 y, 73% males, n=485) and the other consisting of 20 y younger nonobese healthy females (n=74).


METHODS
Genotyping for the -174 IL-6 G/C and the -572 G/C SNPs, body mass index (BMI), serum leptin levels, serum IL-6 levels, C-reactive protein, fasting blood glucose and various blood lipids.


RESULTS
The common -174 C allele (f(C)=0.46), but not any -572 allele, was associated with higher BMI and higher serum leptin levels in both study populations. In the larger population, there were significant odds ratios for the association of CC (2.13) and GC (1.76) genotypes with overweight (BMI>25 kg/m(2)). Moreover, as the C allele was common, it accounted for a significant population-attributable risk of overweight (12%; CI 2-21%), although its average effect was modest in this sample.


CONCLUSIONS
Genetically determined individual differences in production of IL-6 may be relevant for the regulation of body fat mass.
Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden.
I
I
Wernstedt
A-L
AL
Eriksson
A
A
Berndtsson
J
J
Hoffstedt
S
S
Skrtic
T
T
Hedner
L M
LM
Hultén
O
O
Wiklund
C
C
Ohlsson
J-O
JO
Jansson
D000328:Adult; D015992:Body Mass Index; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D015850:Interleukin-6; D020738:Leptin