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A Single-Nucleotide Polymorphism in the p110β Gene Promoter Is Associated with Partial Protection from Insulin Resistance in Severely Obese Adolescents

Department of Pediatric Endocrinology (C.L.S., P.B.), Pôle d’Endocrinologie Enfants-Adultes Cochin-St. Vincent de Paul, APHP, Hôpital Saint Vincent de Paul, Paris V University, and Institut National de la Santé et de la Recherche Médicale U561 (C.L.S., P.B.), Hôpital Saint Vincent de Paul, 75014 Paris, France; Service de Biostatistique et d’Information Médicale (A.D.), Hôpital Necker, 75015 Paris, France; Department of Pediatrics (E.M.D.G.), Second University of Naples, 80138 Naples, Italy; and Centre National de la Recherche Scientifique UMR8090 (P.F.), Pasteur Institute, 59021 Lille, France

Address all correspondence and requests for reprints to: Pierre Bougnères, Pediatric Endocrinology, Hôpital Saint Vincent de Paul, 82 Avenue Denfert Rochereau, 75014 Paris, France. E-mail: pierre.bougneres{at}wanadoo.fr.

Objective: Severe juvenile obesity causes metabolic and cardiovascular complications in adulthood. The catalytic p110β subunit of phosphatidyl-inositol-3 kinase is a major effector of insulin action. We studied the p110β gene as a candidate gene for association with insulin resistance (IR) and fasting glycemia in severely obese children.

Methods: We conducted an association study in 580 severely obese European children (body mass index > 99.6th centile) and 606 nonobese control children, in whom glucose and insulin were measured in the fasting state. The homeostasis model assessment insulin resistance index was used to estimate IR.

Results: We found that a single-nucleotide polymorphism (rs361072) located in the promoter of the p110β gene was associated with fasting glucose (P = 0.0002), insulin (P = 2.6 10^–8), and homeostasis model assessment insulin resistance index (P =1 10^–9) in the severely obese children. The effect of rs361072 was marginal or not significant in nonobese children.

Conclusions: The C allele of rs361072 attenuates IR in superobese children.