Original Article

International Journal of Obesity (2009) 33, 525–533; doi:10.1038/ijo.2009.47; published online 17 March 2009

Variants of the interleukin-1 receptor antagonist gene are associated with fat mass in men

N Andersson1, L Strandberg1, S Nilsson2, Ö Ljungren3, M K Karlsson4,5, D Mellström6, M Lorentzon6, C Ohlsson6 and J-O Jansson1

  1. 1Department of Neuroscience and Physiology/Endocrinology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  2. 2Mathematical Statistics, Chalmers University of Technology, Gothenburg, Sweden
  3. 3Department of Medical Sciences, University of Uppsala, Uppsala, Sweden
  4. 4Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden
  5. 5Department of Orthopedics, Malmö University Hospital, Malmö, Sweden
  6. 6Departments of Geriatrics and Internal Medicine, Center for Bone Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Correspondence: Professor J-O Jansson, Department of Neuroscience and Physiology/Endocrinology, Sahlgrenska Academy at University of Gothenburg, Box 434, Göteborg SE-405 30, Sweden. E-mail: JOJ@medic.gu.se

Received 20 November 2008; Revised 4 February 2009; Accepted 14 February 2009; Published online 17 March 2009.

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Abstract

Context:

 

Immune functions seem to have connections to variations in body fat mass. Studies of knockout mice indicate that endogenous interleukin (IL)-1 can suppress mature-onset obesity.

Objective:

 

To systematically investigate our hypotheses that single-nucleotide polymorphisms (SNPs) and/or haplotypes variants in the IL-1 gene system are associated with fat mass.

Subjects:

 

The Gothenburg osteoporosis and obesity determinants (GOOD) study is a population-based cross-sectional study of 18–20 year-old men (n=1068), from Gothenburg, Sweden. Major findings were confirmed in elderly men (n=3014) from the Swedish part of the osteoporotic fractures in men (MrOS) multicenter population-based study.

Main Outcome Measure:

 

The genotype distributions and their association with body fat mass in different compartments, measured with dual-energy X-ray absorptiometry (DXA).

Results:

 

Out of 15 investigated SNPs in the IL-1 receptor antagonist (IL1RN) gene, a recently identified 3′ untranslated region C>T (rs4252041, minor allele frequency=4%) SNP was associated with the primary outcome total fat mass (P=0.003) and regional fat masses, but not with lean body mass or serum IL-1 receptor 1 (IL1RN) levels. This SNP was also associated with body fat when correcting the earlier reported IL1RN+2018 T>C (rs419598) SNP (in linkage disequilibrium with a well-studied variable number tandem repeat of 86bp). The association between rs4252041 SNP and body fat was confirmed in the older MrOS population (P=0.03). The rs4252041 SNP was part of three haplotypes consisting of five adjacent SNPs that were identified by a sliding window approach. These haplotypes had a highly significant global association with total body fat (P<0.001). None of the other investigated members of the IL-1 gene family displayed any SNPs that have not been described previously to be significantly associated with body fat.

Conclusions:

 

The IL1RN gene, shown to enhance obesity by suppressing IL-1 effects in experimental animals, have no previously described gene polymorphisms and haplotypes that are associated with fat, but not lean mass in two populations of men.

Keywords:

anakinra, single-nucleotide polymorphism, dual-energy X-ray absorptiometry

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