Early Detrimental Metabolic Outcomes of rs17300539-A Allele of ADIPOQ Gene Despite Higher Adiponectinemia

Authors

  • Anita Morandi,

    Corresponding author
    1. Centre National de la Recherche Scientifique UMR8090, Pasteur Institute of Lille, Lille, France
    2. Regional Centre for Juvenile Diabetes, Obesity and Clinical Nutrition, Verona, Italy
    Search for more papers by this author
  • Claudio Maffeis,

    1. Regional Centre for Juvenile Diabetes, Obesity and Clinical Nutrition, Verona, Italy
    2. Department of Mother and Child, Biology-Genetics, Section of Paediatrics, University of Verona, Verona, Italy
    Search for more papers by this author
  • Stéphane Lobbens,

    1. Centre National de la Recherche Scientifique UMR8090, Pasteur Institute of Lille, Lille, France
    Search for more papers by this author
  • Nabila Bouatia-Naji,

    1. Centre National de la Recherche Scientifique UMR8090, Pasteur Institute of Lille, Lille, France
    Search for more papers by this author
  • Barbara Heude,

    1. INSERM U 780, IFR 69, Faculté de Médecine Paris-Sud, Villejuif, France
    Search for more papers by this author
  • Leonardo Pinelli,

    1. Regional Centre for Juvenile Diabetes, Obesity and Clinical Nutrition, Verona, Italy
    2. Department of Mother and Child, Biology-Genetics, Section of Paediatrics, University of Verona, Verona, Italy
    Search for more papers by this author
  • David Meyre,

    1. Centre National de la Recherche Scientifique UMR8090, Pasteur Institute of Lille, Lille, France
    Search for more papers by this author
  • Philippe Froguel

    1. Centre National de la Recherche Scientifique UMR8090, Pasteur Institute of Lille, Lille, France
    2. Genomic Medicine and Genome Centre, Hammersmith Campus, Imperial College, London, UK
    Search for more papers by this author

(anita.morandi@good.ibl.fr)

Abstract

Minor allele A of single-nucleotide polymorphism (SNP) 11391 G/A of ADIPOQ gene (rs17300539) has been consistently associated with higher adiponectin levels in adults and children. The aim of this study was to investigate the metabolic role of this variant in a large cohort of children of European origin. A total of 1,852 children from two general populations in Verona and in Fleurbaix–Laventie and from the Lille childhood obesity cohort, were genotyped and pooled together after checking for the absence of genetic heterogeneity for rs17300539 between Italian and French children. The genotype of rs17300539 was studied in relation to circulating adiponectin levels, BMI, fasting plasma glucose, fasting serum insulin (FSI), insulin resistance index (homeostasis model assessment of insulin resistance (HOMAIR)), high-density lipoprotein cholesterol, and triglycerides. After adjustment for known confounders, rs17300539 GA+AA carriers had 1.6 µg/ml higher adiponectin levels (P = 6 × 10−8) than GG carriers. They also showed higher BMI (B = 0.97, P = 0.015) and higher prevalence of obesity (OR = 1.35 (1.06–1.85), P = 0.015) than GG carriers. Before adjusting for obesity status, GA+AA carriers had higher FSI (B = 1.10, P = 0.040) and higher HOMAIR (B = 0.31, P = 0.020) than GG carriers. After adjustment for obesity status, they did not differ from GG carriers for any metabolic parameter, either among obese or nonobese children. The rs17300539-A variant, though consistently associated with higher adiponectin levels, does not exert any appreciable protective metabolic effect in children, either in the presence or absence of obesity. In contrast, this SNP may increase the risk for childhood obesity and related insulin resistance.

Ancillary