A single-nucleotide polymorphism in the p110beta gene promoter is associated with partial protection from insulin resistance in severely obese adolescents.
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.
Le Stunff
Catherine
C
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.
Dechartres
Agnès
A
Miraglia Del Giudice
Emanuele
E
Froguel
Philippe
P
Bougnères
Pierre
P
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
D001786:Blood Glucose; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C497132:PIK3CB protein, human