title: Impact of phosphodiesterase 8B gene rs4704397 variation on thyroid homeostasis in childhood obesity.
abstract: BACKGROUND
  Several studies demonstrated that obese children have higher TSH than normal-weight children. The polymorphism rs4704397 in the phosphodiesterase 8B (PDE8B) gene showed an association with TSH.
  
  
  OBJECTIVE
  i) To assess the effect of PDE8B on TSH in obese children; ii) to dissect the role of obesity degree in modulating this association; and iii) to stratify the individual risk to show hyperthyrotropinaemia according to PDE8B genotype.
  
  
  METHODS
  Eight hundred and sixty-seven Italian obese children were investigated. Clinical data and thyroid hormones were evaluated and the PDE8B rs4704397 was genotyped.
  
  
  RESULTS
  PDE8B A/A homozygous subjects showed higher TSH (P=0.0005) compared with A/G or G/G. No differences were found for peripheral thyroid hormones. Among A/A children, 22% had hyperthyrotropinaemia, compared with 11.6% of heterozygotes and 10.8% of G/G (P=0.0008). Consistently, A/A had an odds ratio (OR) to show abnormal TSH level of 2.25 (P=0.0004). Body mass index (BMI) appeared correlated with TSH (P=0.0001), but the strength of the effect of PDE8B on TSH was independent of BMI (P=0.1). Children were subdivided into six groups according to obesity degree and genotypes. PDE8B A/A with BMI SDS above 3 had the highest OR (OR 2.6, P=0.0015) to have hyperthyrotropinaemia, whereas G/G with BMI SDS below 3 showed the lowest possibilities (OR 0.3, P=0.005).
  
  
  CONCLUSIONS
  We have shown: i) in obese children, PDE8B is associated with TSH; ii) the interaction between adiposity and PDE8B on TSH is not synergistic, but follows an additive model; and iii) impact of this association in the stratification of individual risk to have hyperthyrotropinaemia.
authors.affiliation: Department of Pediatrics F. Fede, Seconda Università degli Studi di Napoli, Via Luigi De Crecchio 2, 80138 Napoli, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Grandone
authors.forename: Laura
authors.initials: L
authors.lastname: Perrone
authors.forename: Grazia
authors.initials: G
authors.lastname: Cirillo
authors.forename: Anna
authors.initials: A
authors.lastname: Di Sessa
authors.forename: Alberto Maria
authors.initials: AM
authors.lastname: Corona
authors.forename: Alessandra
authors.initials: A
authors.lastname: Amato
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Cresta
authors.forename: Tiziana
authors.initials: T
authors.lastname: Romano
authors.forename: Emanuele
authors.initials: E
authors.lastname: Miraglia del Giudice
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics*; D000293:Adolescent; D017668:Age of Onset; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000502:physiology; D006706:Homeostasis / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007037:Hypothyroidism / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D008297:Male; D009765:Obesity / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000502:physiology*; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism
chemical_list: D013972:Thyrotropin; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C468781:PDE8B protein, human