Variants of the interleukin-1 receptor antagonist gene are associated with fat mass in men.
Int J Obes (Lond)
; 33(5): 525-33, 2009 May.
Article
in En
| MEDLINE
| ID: mdl-19290009
ABSTRACT
CONTEXT 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.SUBJECTS:
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. MAIN OUTCOMEMEASURE:
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Haplotypes
/
Adipose Tissue
/
Polymorphism, Single Nucleotide
/
Interleukin 1 Receptor Antagonist Protein
Type of study:
Clinical_trials
/
Observational_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Humans
/
Male
Country/Region as subject:
Europa
Language:
En
Journal:
Int J Obes (Lond)
Journal subject:
METABOLISMO
Year:
2009
Document type:
Article
Affiliation country:
Suecia
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM