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

Niklas Andersson (Institutionen för medicin, avdelningen för invärtesmedicin ; Institutionen för kemi- och bioteknik, Livsmedelsvetenskap) ; Louise Strandberg ; Staffan Nilsson (Institutionen för matematiska vetenskaper, matematisk statistik) ; Svetlana Adamovic ; M. K. Karlsson ; O. Ljunggren ; Dan Mellström ; N. E. Lane ; J. M. Zmuda ; C. Nielsen ; E. Orwoll ; Mattias Lorentzon ; Claes Ohlsson ; John-Olov Jansson
International Journal of Obesity (0307-0565). Vol. 34 (2010), 6, p. 1011-9.
[Artikel, refereegranskad vetenskaplig]

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.

Nyckelord: Absorptiometry, Photon, Adiposity/*genetics, Adolescent, Aged, Body Mass Index, Cross-Sectional Studies, European Continental Ancestry Group/genetics, Gene Frequency/genetics/physiology, Genetic Variation/genetics, Genotype, Humans, Interleukin-6/*genetics/physiology, Male, Obesity/*genetics/physiopathology, Polymorphism, Single Nucleotide/*genetics, Receptors, Interleukin-6/*genetics/physiology, Sweden, Young Adult

Denna post skapades 2014-05-18. Senast ändrad 2015-01-16.
CPL Pubid: 198231


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Institutioner (Chalmers)

Institutionen för medicin, avdelningen för invärtesmedicin (2006-2011)
Institutionen för kemi- och bioteknik, Livsmedelsvetenskap (2005-2014)
Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi (GU)
Institutionen för matematiska vetenskaper, matematisk statistik (2005-2016)
Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik (GU)
Institutionen för medicin (GU)


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