Variants of the interleukin-1 receptor antagonist gene are associated with fat mass in men.
BACKGROUND
Immune functions seem to have connections to variations in body fat mass. Studies of knockout mice indicate that endogenous interleukin (IL)-1 can suppress mature-onset obesity.


OBJECTIVE
To systematically investigate our hypotheses that single-nucleotide polymorphisms (SNPs) and/or haplotypes variants in the IL-1 gene system are associated with fat mass.


METHODS
The Gothenburg osteoporosis and obesity determinants (GOOD) study is a population-based cross-sectional study of 18-20 year-old men (n=1068), from Gothenburg, Sweden. Major findings were confirmed in elderly men (n=3014) from the Swedish part of the osteoporotic fractures in men (MrOS) multicenter population-based study.


METHODS
The genotype distributions and their association with body fat mass in different compartments, measured with dual-energy X-ray absorptiometry (DXA).


RESULTS
Out of 15 investigated SNPs in the IL-1 receptor antagonist (IL1RN) gene, a recently identified 3' untranslated region C>T (rs4252041, minor allele frequency=4%) SNP was associated with the primary outcome total fat mass (P=0.003) and regional fat masses, but not with lean body mass or serum IL-1 receptor 1 (IL1RN) levels. This SNP was also associated with body fat when correcting the earlier reported IL1RN+2018 T>C (rs419598) SNP (in linkage disequilibrium with a well-studied variable number tandem repeat of 86 bp). The association between rs4252041 SNP and body fat was confirmed in the older MrOS population (P=0.03). The rs4252041 SNP was part of three haplotypes consisting of five adjacent SNPs that were identified by a sliding window approach. These haplotypes had a highly significant global association with total body fat (P<0.001). None of the other investigated members of the IL-1 gene family displayed any SNPs that have not been described previously to be significantly associated with body fat.


CONCLUSIONS
The IL1RN gene, shown to enhance obesity by suppressing IL-1 effects in experimental animals, have not [corrected] previously described gene polymorphisms and haplotypes that are associated with fat, but not lean mass in two populations of men.
Andersson
N
N
Department of Neuroscience and Physiology/Endocrinology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Strandberg
L
L
Nilsson
S
S
Ljungren
O
O
Karlsson
M K
MK
Mellström
D
D
Lorentzon
M
M
Ohlsson
C
C
Jansson
J-O
JO
D015502:Absorptiometry, Photon; D000273:Adipose Tissue; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D006239:Haplotypes; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D013548:Sweden; D055815:Young Adult
D053590:Interleukin 1 Receptor Antagonist Protein