Variants of the interleukin-1 receptor antagonist gene are associated with fat mass in men.
Artikel i vetenskaplig tidskrift, 2009

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 86 bp). 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.International Journal of Obesity advance online publication, 17 March 2009; doi:10.1038/ijo.2009.47.

Författare

Niklas Andersson

Göteborgs universitet

Louise Grahnemo

Göteborgs universitet

Staffan Nilsson

Chalmers, Matematiska vetenskaper, Matematisk statistik

Göteborgs universitet

Ö Ljungren

Uppsala universitet

Magnus K Karlsson

Lunds universitet

Skånes universitetssjukhus (SUS)

Dan Mellström

Göteborgs universitet

Mattias Lorentzon

Göteborgs universitet

Claes Ohlsson

Göteborgs universitet

John-Olov Jansson

Göteborgs universitet

International Journal of Obesity

0307-0565 (ISSN) 1476-5497 (eISSN)

Vol. 33 5 525-533

Ämneskategorier

Fysiologi

DOI

10.1038/ijo.2009.47

PubMed

19290009

Mer information

Senast uppdaterat

2018-05-14