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

作者：Andersson N; Strandberg L; Nilsson S; Adamovic S; Karlsson M K; Ljunggren O; Mellstrom D; Lane N E; Zmuda J M; Nielsen C; Orwoll E; Lorentzon M; Ohlsson C; Jansson J O^*

来源：International Journal of Obesity, 2010, 34(6): 1011-1019.

DOI：10.1038/ijo.2010.27

• IL6
• IL6R
• SNP
• rs10242595

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

• 出版日期2010-6