title: Variants of the interleukin-1 receptor antagonist gene are associated with fat mass in men.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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 not [corrected] previously described gene polymorphisms and haplotypes that are associated with fat, but not lean mass in two populations of men.
authors.affiliation: Department of Neuroscience and Physiology/Endocrinology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Andersson
authors.forename: L
authors.initials: L
authors.lastname: Strandberg
authors.forename: S
authors.initials: S
authors.lastname: Nilsson
authors.forename: O
authors.initials: O
authors.lastname: Ljungren
authors.forename: M K
authors.initials: MK
authors.lastname: Karlsson
authors.forename: D
authors.initials: D
authors.lastname: Mellström
authors.forename: M
authors.initials: M
authors.lastname: Lorentzon
authors.forename: C
authors.initials: C
authors.lastname: Ohlsson
authors.forename: J-O
authors.initials: JO
authors.lastname: Jansson
mesh_terms: D015502:Absorptiometry, Photon; D000273:Adipose Tissue; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D006239:Haplotypes; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D013548:Sweden; D055815:Young Adult
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein