ACDC/adiponectin polymorphisms are associated with severe childhood and adult obesity.
Common single nucleotide polymorphisms (SNPs) in the ACDC adiponectin encoding gene have been associated with insulin resistance and type 2 diabetes in several populations. Here, we investigate the role of SNPs -11,377C > G, -11,391G > A, +45T > G, and +276G > T in 2,579 French Caucasians (1,229 morbidly obese and 1,350 control subjects). We found an association between severe forms of obesity and -11,377C (odds ratio 1.23, P = 0.001) and +276T (1.19, P = 0.006). Surprisingly, alternative alleles -11,377G and +276G have been previously reported as risk factors for type 2 diabetes. Transmission disequilibrium tests showed a trend in overtransmission (56.7%) of a risk haplotype 1((C))-1((G))-1((T))-2((T)) including -11,377C and +276T in 634 obesity trios (P = 0.097). Family-based analysis in 400 trios from the general population indicated association between obesity haplotype and higher adiponectin levels, suggesting a role of hyperadiponectinemia in weight gain. However, experiments studying the putative roles of SNPs -11,377C > G and +276G > T on ACDC functionality were not conclusive. In contrast, promoter SNP -11,391G > A was associated with higher adiponectin levels in obese children (P = 0.005) and in children from the general population (0.00007). In vitro transcriptional assays showed that -11,391A may increase ACDC activity. In summary, our study suggests that variations at the ACDC/adiponectin gene are associated with risk of severe forms of obesity. However, the mechanisms underlying these possible associations are not fully understood.
Bouatia-Naji
Nabila
N
Centre National de la Recherche Scientifique UMR8090, Pasteur Institute of Lille, France.
Meyre
David
D
Lobbens
Stéphane
S
Séron
Karin
K
Fumeron
Frédéric
F
Balkau
Beverley
B
Heude
Barbara
B
Jouret
Béatrice
B
Scherer
Philipp E
PE
Dina
Christian
C
Weill
Jacques
J
Froguel
Philippe
P
D052242:Adiponectin / Q000097:blood / Q000235:genetics; D000328:Adult; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D006239:Haplotypes; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
C499918:ADIPOQ protein, human; D052242:Adiponectin