Association Analysis Indicates That a Variant GATA-Binding Site in the PIK3CB Promoter Is a Cis-Acting Expression Quantitative Trait Locus for This Gene and Attenuates Insulin Resistance in Obese Children

Association Analysis Indicates That a Variant GATA-Binding Site in the PIK3CB Promoter Is a Cis-Acting Expression Quantitative Trait Locus for This Gene and Attenuates Insulin Resistance in Obese Children Catherine Le Stunff 1 2 , Agnès Dechartres 3 , Virginie Mariot 2 , Chantal Lotton 2 , Cecelia Trainor 4 , Emanuele Miraglia Del Giudice 5 , David Meyre 6 , Ivan Bieche 7 , Ingrid Laurendeau 7 , Philippe Froguel 6 , Diana Zelenika 8 , Dani Fallin 9 , Mark Lathrop 8 , Paul-Henri Roméo 10 and Pierre Bougnères 1 2 1 Pediatric Endocrinology, Pôle d'Endocrinologie Enfants-Adultes Cochin-St Vincent de Paul, Assistance Publique-Hôspitaux de Paris, Hôpital Saint Vincent de Paul, Paris V University, Paris, France 2 Institut National de la Santé et de la Recherche Médicale (INSERM) U561, Hôpital Saint Vincent de Paul, Paris, France 3 Service de Biostatistique, Hôpital Necker, Paris, France 4 Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 5 Department of Pediatrics, Second University of Naples, Naples, Italy 6 Centre National de la Recherche Scientifique UMR8090, Pasteur Institute, Lille, France 7 INSERM U745, Faculty of Pharmacy, Paris V, Paris, France 8 Centre National de Génotypage, Genomic Center of the Commissariat de l’Energie Atomique, Evry, France 9 Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 10 Institut de Radiobiologie Cellulaire et Moléculaire, Département des Sciences du Vivant of the Commissariat de l’Energie Atomique, Fontenay aux Roses, France Address correspondence and reprint requests to Pierre Bougnères, Pediatric Endocrinology, Hôpital Saint Vincent de Paul, 82 Ave. Denfert Rochereau, 75014 Paris, France. E-mail: bougneres{at}paris5.inserm.fr Abstract OBJECTIVE— In search of functional polymorphisms associated with the genetics of insulin resistance, we studied a variant in the promoter of PIK3CB , the gene coding for the catalytic p110β subunit of phosphatidylinositol (PI) 3-kinase, a major effector of insulin action. RESEARCH DESIGN AND METHODS— The rs361072 C/T variant was selected among single nucleotide polymorphisms of the PIK3CB region because we suspected that its common C allele (allelic frequency ∼50% in Europeans) could create a GATA-binding motif and was genotyped in five cohorts of obese ( n = 1,876) and two cohorts of nonobese ( n = 1,490) European children. To estimate