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A variant near the interleukin-6 gene is associated with fat mass in Caucasian men

Andersson, N. ; Strandberg, L. ; Nilsson, S. ; Adamovic, S. ; Karlsson, Magnus LU ; Ljunggren, O. ; Mellstrom, D. ; Lane, N. E. ; Zmuda, J. M. and Nielsen, C. , et al. (2010) In International Journal of Obesity 34(6). p.1011-1019
Abstract
Context: Regulation of fat mass appears to be associated with immune functions. Studies of knockout mice show that endogenous interleukin (IL)-6 can suppress mature-onset obesity. Objective: To systematically investigate associations of single nucleotide polymorphisms (SNPs) near the IL-6 (IL6) and IL-6 receptor (IL6R) genes with body fat mass, in support for our hypothesis that variants of these genes can be associated with obesity. Design and Study Subjects: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-year-old men (n = 1049), from the Gothenburg area (Sweden). Major findings were confirmed in two additional cohorts consisting of elderly men from the... (More)
Context: Regulation of fat mass appears to be associated with immune functions. Studies of knockout mice show that endogenous interleukin (IL)-6 can suppress mature-onset obesity. Objective: To systematically investigate associations of single nucleotide polymorphisms (SNPs) near the IL-6 (IL6) and IL-6 receptor (IL6R) genes with body fat mass, in support for our hypothesis that variants of these genes can be associated with obesity. Design and Study Subjects: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-year-old men (n = 1049), from the Gothenburg area (Sweden). Major findings were confirmed in two additional cohorts consisting of elderly men from the Osteoporotic Fractures in Men (MrOS) Sweden (n = 2851) and MrOS US (n = 5611) multicenter population-based studies. Main Outcome: The genotype distributions and their association with fat mass in different compartments, measured with dual-energy X-ray absorptiometry. Results: Out of 18 evaluated tag SNPs near the IL6 and IL6R genes, a recently identified SNP rs10242595 G/A (minor allele frequency = 29%) 3' of the IL6 gene was negatively associated with the primary outcome total body fat mass (effect size -0.11 standard deviation (s.d.) units per A allele, P-0.02). This negative association with fat mass was also confirmed in the combined MrOS Sweden and MrOS US cohorts (effect size -0.05 s.d. units per A allele, P = 0.002). When all three cohorts were combined (n = 8927, Caucasian subjects), rs10242595*A showed a negative association with total body fat mass (effect size -0.05 s.d. units per A allele, P<0.0002). Furthermore, the rs10242595*A was associated with low body mass index (effect size -0.03, P<0.001) and smaller regional fat masses. None of the other SNPs investigated in the GOOD study were reproducibly associated with body fat. Conclusions: The IL6 gene polymorphism rs10242595*A is associated with decreased fat mass in three combined cohorts of 8927 Caucasian men. International Journal of Obesity (2010) 34, 1011-1019; doi:10.1038/ijo.2010.27; published online 16 February 2010 (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
rs10242595, SNP, IL6, IL6R
in
International Journal of Obesity
volume
34
issue
6
pages
1011 - 1019
publisher
Nature Publishing Group
external identifiers
  • wos:000278663500008
  • scopus:77953612512
  • pmid:20157327
ISSN
1476-5497
DOI
10.1038/ijo.2010.27
language
English
LU publication?
yes
id
6a727f18-3c18-4d2b-b04a-bab98c0e177e (old id 1630999)
date added to LUP
2016-04-01 10:16:40
date last changed
2022-01-25 21:39:23
@article{6a727f18-3c18-4d2b-b04a-bab98c0e177e,
  abstract     = {{Context: Regulation of fat mass appears to be associated with immune functions. Studies of knockout mice show that endogenous interleukin (IL)-6 can suppress mature-onset obesity. Objective: To systematically investigate associations of single nucleotide polymorphisms (SNPs) near the IL-6 (IL6) and IL-6 receptor (IL6R) genes with body fat mass, in support for our hypothesis that variants of these genes can be associated with obesity. Design and Study Subjects: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-year-old men (n = 1049), from the Gothenburg area (Sweden). Major findings were confirmed in two additional cohorts consisting of elderly men from the Osteoporotic Fractures in Men (MrOS) Sweden (n = 2851) and MrOS US (n = 5611) multicenter population-based studies. Main Outcome: The genotype distributions and their association with fat mass in different compartments, measured with dual-energy X-ray absorptiometry. Results: Out of 18 evaluated tag SNPs near the IL6 and IL6R genes, a recently identified SNP rs10242595 G/A (minor allele frequency = 29%) 3' of the IL6 gene was negatively associated with the primary outcome total body fat mass (effect size -0.11 standard deviation (s.d.) units per A allele, P-0.02). This negative association with fat mass was also confirmed in the combined MrOS Sweden and MrOS US cohorts (effect size -0.05 s.d. units per A allele, P = 0.002). When all three cohorts were combined (n = 8927, Caucasian subjects), rs10242595*A showed a negative association with total body fat mass (effect size -0.05 s.d. units per A allele, P&lt;0.0002). Furthermore, the rs10242595*A was associated with low body mass index (effect size -0.03, P&lt;0.001) and smaller regional fat masses. None of the other SNPs investigated in the GOOD study were reproducibly associated with body fat. Conclusions: The IL6 gene polymorphism rs10242595*A is associated with decreased fat mass in three combined cohorts of 8927 Caucasian men. International Journal of Obesity (2010) 34, 1011-1019; doi:10.1038/ijo.2010.27; published online 16 February 2010}},
  author       = {{Andersson, N. and Strandberg, L. and Nilsson, S. and Adamovic, S. and Karlsson, Magnus and Ljunggren, O. and Mellstrom, D. and Lane, N. E. and Zmuda, J. M. and Nielsen, C. and Orwoll, E. and Lorentzon, M. and Ohlsson, C. and Jansson, J-O}},
  issn         = {{1476-5497}},
  keywords     = {{rs10242595; SNP; IL6; IL6R}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{1011--1019}},
  publisher    = {{Nature Publishing Group}},
  series       = {{International Journal of Obesity}},
  title        = {{A variant near the interleukin-6 gene is associated with fat mass in Caucasian men}},
  url          = {{http://dx.doi.org/10.1038/ijo.2010.27}},
  doi          = {{10.1038/ijo.2010.27}},
  volume       = {{34}},
  year         = {{2010}},
}