title: ACDC/adiponectin polymorphisms are associated with severe childhood and adult obesity.
abstract: 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.
authors.affiliation: Centre National de la Recherche Scientifique UMR8090, Pasteur Institute of Lille, France.
authors.forename: Nabila
authors.initials: N
authors.lastname: Bouatia-Naji
authors.forename: David
authors.initials: D
authors.lastname: Meyre
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lobbens
authors.forename: Karin
authors.initials: K
authors.lastname: Séron
authors.forename: Frédéric
authors.initials: F
authors.lastname: Fumeron
authors.forename: Beverley
authors.initials: B
authors.lastname: Balkau
authors.forename: Barbara
authors.initials: B
authors.lastname: Heude
authors.forename: Béatrice
authors.initials: B
authors.lastname: Jouret
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
authors.forename: Christian
authors.initials: C
authors.lastname: Dina
authors.forename: Jacques
authors.initials: J
authors.lastname: Weill
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
mesh_terms: 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
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin