ACDC/adiponectin polymorphisms are associated with severe childhood and adult obesity

Nabila Bouatia-Naji, David Meyre, Stéphane Lobbens, Karin Séron, Frédéric Fumeron, Beverley Balkau, Barbara Heude, Béatrice Jouret, Philipp E. Scherer, Christian Dina, Jacques Weill, Philippe Froguel

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)545-550
Number of pages6
JournalDiabetes
Volume55
Issue number2
DOIs
StatePublished - Feb 2006

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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