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 not [corrected] previously described gene polymorphisms and haplotypes that are associated with fat, but not lean mass in two populations of men.
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 not [corrected] previously described gene polymorphisms and haplotypes that are associated with fat, but not lean mass in two populations of men.
Authors: N Andersson; L Strandberg; S Nilsson; S Adamovic; M K Karlsson; O Ljunggren; D Mellström; N E Lane; J M Zmuda; C Nielsen; E Orwoll; M Lorentzon; C Ohlsson; J-O Jansson Journal: Int J Obes (Lond) Date: 2010-02-16 Impact factor: 5.095
Authors: Christian Herder; Marja-Liisa Nuotio; Sonia Shah; Stefan Blankenberg; Eric J Brunner; Maren Carstensen; Christian Gieger; Harald Grallert; Antti Jula; Mika Kähönen; Johannes Kettunen; Mika Kivimäki; Wolfgang Koenig; Kati Kristiansson; Claudia Langenberg; Terho Lehtimäki; Kari Luotola; Carola Marzi; Christian Müller; Annette Peters; Holger Prokisch; Olli Raitakari; Wolfgang Rathmann; Michael Roden; Marko Salmi; Katharina Schramm; Daniel Swerdlow; Adam G Tabak; Barbara Thorand; Nick Wareham; Philipp S Wild; Tanja Zeller; Aroon D Hingorani; Daniel R Witte; Meena Kumari; Markus Perola; Veikko Salomaa Journal: Diabetes Date: 2014-06-26 Impact factor: 9.461