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Interleukin-1 System Gene Polymorphisms Are Associated with Fat Mass in Young Men

Institute of Neuroscience and Physiology/Endocrinology (L.S., V.W., J.-O.J.), Sahlgrenska Academy, and Swegene Bioinformatics (A.H., S.N.), Göteborg University, SE-405 30 Göteborg, Sweden; and Center for Bone Research at the Sahlgrenska Academy, Sahlgrenska University Hospital (M.L., C.O.), SE-413 45 Göteborg, Sweden

Address all correspondence and requests for reprints to: John-Olov Jansson, M.D., Ph.D., Institute of Neuroscience and Physiology/Endocrinology, Sahlgrenska Academy, Göteborg University, P.O. Box 434, SE 405 30 Göteborg, Sweden. E-mail: joj{at}medic.gu.se.

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-1ß +3953 C/T, IL-1ß-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-1ß 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-1ß-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.

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