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A common polymorphism in the interleukin-6 gene promoter is associated with overweight

Journal article
Authors Ingrid Wernstedt
Anna-Lena Eriksson
Anna Berndtsson
J Hoffstedt
Stanko Skrtic
Thomas Hedner
Lillemor Mattsson Hultén
Olov Wiklund
Claes Ohlsson
John-Olov Jansson
Published in Int J Obes Relat Metab Disord
Volume 28
Issue 10
Pages 1272-9
Publication year 2004
Published at Wallenberg Laboratory
Institute of Physiology and Pharmacology, Dept of Pharmacology
Institute of Internal Medicine, Dept of Medicine
Institute of Internal Medicine
Institute of Internal Medicine, Dept of Body Composition and Metabolism
Institute of Internal Medicine, Dept of Clinical Pharmacology
Pages 1272-9
Language en
Links www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords Adult, Body Mass Index, Female, *Genetic Predisposition to Disease, Genotype, Humans, Interleukin-6/blood/*genetics, Leptin/blood, Male, Middle Aged, Obesity/*genetics, *Polymorphism, Genetic, *Promoter Regions (Genetics)
Subject categories Medical and Health Sciences

Abstract

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. DESIGN: Trans-sectional association study of IL-6 gene promoter SNPs and indices of obesity. SUBJECTS: 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). MEASUREMENTS: 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. CONCLUSION: Genetically determined individual differences in production of IL-6 may be relevant for the regulation of body fat mass.

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