A variant near the interleukin-6 gene is associated with fat mass in Caucasian men
Artikel i vetenskaplig tidskrift, 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.

Polymorphism

Male

Absorptiometry

European Continental Ancestry Group/genetics

Sweden

Adolescent

Interleukin-6/*genetics/physiology

Young Adult

Humans

Genetic Variation/genetics

Single Nucleotide/*genetics

Obesity/*genetics/physiopathology

Gene Frequency/genetics/physiology

Aged

Receptors

Cross-Sectional Studies

Photon

Adiposity/*genetics

Genotype

Interleukin-6/*genetics/physiology

Body Mass Index

Författare

Niklas Andersson

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Livsmedelsvetenskap

Göteborgs universitet

Louise Grahnemo

Göteborgs universitet

Staffan Nilsson

Chalmers, Matematiska vetenskaper, matematisk statistik

Göteborgs universitet

Svetlana Adamovic

Göteborgs universitet

Magnus K Karlsson

Skånes universitetssjukhus (SUS)

Lunds universitet

O. Ljunggren

Uppsala universitet

Dan Mellström

Göteborgs universitet

N. E. Lane

University of California

J. M. Zmuda

University of Pittsburgh Graduate School of Public Health

C. Nielsen

Oregon Health and Science University

E. Orwoll

Oregon Health and Science University

Mattias Lorentzon

Göteborgs universitet

Claes Ohlsson

Göteborgs universitet

John-Olov Jansson

Göteborgs universitet

International Journal of Obesity

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

Vol. 34 6 1011-9

Ämneskategorier

Klinisk medicin

DOI

10.1038/ijo.2010.27