title: FKBP5 polymorphism is associated with insulin resistance in children and adolescents with obesity.
abstract: Since metabolic syndrome shares several clinical features with hypercortisolism, it was hypothesised that genes altering individual glucocorticoid (GC) sensitivity might be implicated in pathogenesis of obesity and its adverse outcomes. FKBP5 gene encodes a chaperon protein in the GC receptor (GR) complex, which modulates steroid action upon target genes. Its functional variant, rs1360780, may enhance FKBP5 gene transcription, affect GR signalling and thereby influence the hypothalamo-pituitary-adrenal axis. We investigated the association of rs1360780 with obesity and metabolic characteristics in 250 obese children and adolescents (mean age 12.3±3.6years, BMI ≥95th percentile).
  
  
  
  Anthropometric measurements, body composition, biochemical and hormonal results were analysed. Genotyping of rs1360780 was compared with 568 lean controls.
  
  
  
  Impaired fasting glucose was present in 8.8%, glucose intolerance in 10.4%, diabetes in 2.8% and dyslipidemia in 28.8% obese individuals. Hypertension was diagnosed in 34 out of 143 patients. No difference was found in FKBP5 polymorphism distribution between subjects with obesity and controls (p>0.05). Stratification by rs1360780 revealed no differences in body mass and composition. However, carriers of the minor allele displayed enhanced insulin resistance (p=0.009) and elevated serum triglyceride (p=0.006), whereas cholesterol, HbA1c, and oral glucose challenge results were similar for all genotypes. Morning ACTH and cortisol did not differ but evening cortisol was higher in minor allele carriers (p=0.039), although this association was lost in logistic regression analysis.
  
  
  
  This study does not support the association of FKBP5 with obesity but demonstrates plausible implication of its variant in susceptibility to obesity-related insulin resistance and hypertriglyceridemia.
authors.affiliation: Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 49 Przybyszewskiego, 60-355 Poznan, Poland; Institute of Human Genetics, Polish Academy of Sciences, 32 Strzeszynska, 60-479 Poznan, Poland. Electronic address: mfichna@man.poznan.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Fichna
authors.affiliation: Department of Paediatric Diabetes and Obesity, Poznan University of Medical Sciences, 27/33 Szpitalna, 60-572 Poznan, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Krzyśko-Pieczka
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, 32 Strzeszynska, 60-479 Poznan, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Żurawek
authors.affiliation: Department of Paediatric Diabetes and Obesity, Poznan University of Medical Sciences, 27/33 Szpitalna, 60-572 Poznan, Poland.
authors.forename: Bogda
authors.initials: B
authors.lastname: Skowrońska
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, 32 Strzeszynska, 60-479 Poznan, Poland; Department of Oncology, Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, 27/33 Szpitalna, 60-572 Poznan, Poland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Januszkiewicz-Lewandowska
authors.affiliation: Department of Paediatric Diabetes and Obesity, Poznan University of Medical Sciences, 27/33 Szpitalna, 60-572 Poznan, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Fichna
mesh_terms: D000293:Adolescent; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D063766:Pediatric Obesity / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D000099159:Tacrolimus Binding Protein 5
chemical_list: D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5
keywords: Childhood obesity; FKBP5 gene; Insulin resistance; Metabolic syndrome; Polymorphism