Interleukin-1 system gene polymorphisms are associated with fat mass in young men.

CONTEXT

There is growing evidence for interactions between the regulation of body fat and the immune system. Studies of knockout mice indicate that IL-1 has an antiobesity effect.

OBJECTIVE

The objective of the study was to investigate our hypothesis that common polymorphisms of the IL-1 system, which are associated with IL-1 activity, also are associated with fat mass. DESIGN, SETTING, AND STUDY SUBJECTS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-yr-old men (n = 1068), mostly Caucasian, from the Gothenburg area (Sweden). Three different polymorphisms, IL-1beta +3953 C/T, IL-1beta-31 T/C, and IL-1 receptor antagonist (IL-1RN) variable number tandem repeat of 86 bp, were investigated in relation to body fat mass.

MAIN OUTCOME MEASURE

The main outcome measures were genotype distributions and their association with body fat mass in different compartments, measured with dual-energy x-ray absorptiometry.

RESULTS

Carriers of the T variant (CT and TT) of the +3953 C to T (F(T) = 0.25) IL-1beta gene polymorphism had significantly lower total fat mass (P = 0.013) and also significantly reduced arm, leg, and trunk fat, compared with CC individuals. IL-1RN*2 carriers with two repeats of the IL-1RN variable number tandem repeat polymorphism had increased total fat (P = 0.036), serum leptin, and fat of trunk and arm as well as serum levels of IL-1RN and IL-1RN production ex vivo. The IL-1beta-31 polymorphism did not correlate with the fat measurements.

CONCLUSIONS

The IL-1 system, recently shown to affect fat mass in experimental animals, contains gene polymorphisms that are associated with fat mass in young men.