A variant near the interleukin-6 gene is associated with fat mass in Caucasian men
Journal article, 2010

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.

Adiposity/*genetics

Adolescent

Male

Genotype

Body Mass Index

Receptors

Young Adult

Cross-Sectional Studies

Humans

Photon

Polymorphism

Single Nucleotide/*genetics

Genetic Variation/genetics

Sweden

Interleukin-6/*genetics/physiology

Interleukin-6/*genetics/physiology

Gene Frequency/genetics/physiology

Obesity/*genetics/physiopathology

Aged

Absorptiometry

European Continental Ancestry Group/genetics

Author

Niklas Andersson

Chalmers, Chemical and Biological Engineering, Life Sciences, Food and Nutrition Science

University of Gothenburg

Louise Grahnemo

University of Gothenburg

Staffan Nilsson

University of Gothenburg

Chalmers, Mathematical Sciences, Mathematical Statistics

Svetlana Adamovic

University of Gothenburg

Magnus K Karlsson

Lund University

Skåne University Hospital

O. Ljunggren

Uppsala University

Dan Mellström

University of Gothenburg

N. E. Lane

University of California

J. M. Zmuda

University of Pittsburgh

C. Nielsen

Oregon Health and Science University

E. Orwoll

Oregon Health and Science University

Mattias Lorentzon

University of Gothenburg

Claes Ohlsson

University of Gothenburg

John-Olov Jansson

University of Gothenburg

International Journal of Obesity

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

Vol. 34 6 1011-9

Subject Categories

Clinical Medicine

DOI

10.1038/ijo.2010.27

More information

Latest update

9/5/2019 1