title: An INSIG2 polymorphism affects glucose homeostasis in Sardinian obese children and adolescents.
abstract: Allelic variants of a single nucleotide polymorphism (SNP), rs7566605, located approximately 10 kb upstream of the INSIG2 gene have been found in association with body weight and with other clinical features related to obesity in some populations but not in others. Our objective was to test the association of this SNP in obese children and adolescents from the genetically isolated population of Sardinia. We tested the association of rs7566605 with body mass index (BMI) and with serum glucose and insulin concentrations and a surrogate measure of insulin resistance (HOMA-IR) in a cohort of 747 Sardinian obese children and adolescents. A case control analysis was performed using 548 ethnically-matched healthy controls. Allelic frequencies of the SNP were similar between patients and controls. Mean glucose and insulin concentration and mean HOMA-IR values were significantly higher in patients carrying the CC genotype than in the CG and GG carriers. In the patients with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), allele C was significantly more frequent than in controls. Although INSIG2 polymorphisms do not consistently associate with BMI, the observation of an association with glucose concentration would support a role for this gene in the metabolic complications of obesity.
authors.affiliation: Servizio di Endocrinologia Pediatrica, Ospedale Microcitemico, ASL Cagliari, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zavattari
authors.forename: Alberto
authors.initials: A
authors.lastname: Loche
authors.forename: Patrizia
authors.initials: P
authors.lastname: Civolani
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pilia
authors.forename: Loredana
authors.initials: L
authors.lastname: Moi
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Casini
authors.forename: Luigi
authors.initials: L
authors.lastname: Minerba
authors.forename: Sandro
authors.initials: S
authors.lastname: Loche
mesh_terms: D000293:Adolescent; D001786:Blood Glucose; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007558:Italy / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009765:Obesity / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; C467727:INSIG2 protein, human; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins