Impact of phosphodiesterase 8B gene rs4704397 variation on thyroid homeostasis in childhood obesity.

CONTEXT: 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.
OBJECTIVES: 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.