title: A single-nucleotide polymorphism in the p110beta gene promoter is associated with partial protection from insulin resistance in severely obese adolescents.
abstract: OBJECTIVE
  Severe juvenile obesity causes metabolic and cardiovascular complications in adulthood. The catalytic p110beta subunit of phosphatidyl-inositol-3 kinase is a major effector of insulin action. We studied the p110beta 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 p110beta 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.
authors.affiliation: Department of Pediatric Endocrinology, Pôle d'Endocrinologie Enfants-Adultes Cochin-St. Vincent de Paul, APHP, Hôpital Saint Vincent de Paul, Paris V University, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Le Stunff
authors.forename: Agnès
authors.initials: A
authors.lastname: Dechartres
authors.forename: Emanuele
authors.initials: E
authors.lastname: Miraglia Del Giudice
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Pierre
authors.initials: P
authors.lastname: Bougnères
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D058534:Class I Phosphatidylinositol 3-Kinases; D015331:Cohort Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D009767:Obesity, Morbid / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D001786:Blood Glucose; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C497132:PIK3CB protein, human