title: Adiposity blunts the positive relationship of thyrotropin with proprotein convertase subtilisin-kexin type 9 levels in euthyroid subjects.
abstract: BACKGROUND
  Effects of thyroid function status on lipoprotein metabolism may extend into the euthyroid range. Low-density lipoprotein (LDL) metabolism is governed by proprotein convertase subtilisin-kexin type 9 (PCSK9), which down-regulates LDL receptor expression, resulting in higher LDL cholesterol (LDL-C). Here, we tested whether plasma PCSK9 correlates with thyroid function in nonobese and obese euthyroid subjects.
  
  
  METHODS
  We assessed the extent to which plasma PCSK9 is determined by thyrotropin (TSH) in 74 euthyroid subjects (31 women; TSH between 0.5 and 4.0 mU/L and free thyroxine [FT4] between 11.0 and 19.5 pM) with varying degrees of obesity (body mass index [BMI] ranging from 20.2 to 40.4 kg/m(2)).
  
  
  RESULTS
  TSH, FT4, PCSK9, non-high-density lipoprotein cholesterol (non-HDL-C), LDL-C, and apolipoprotein B (apoB) levels were not different between 64 nonobese subjects (BMI<30 kg/m(2)) and 10 obese subjects (BMI≥30 kg/m(2); p>0.20 for each). PCSK9 correlated positively with TSH in nonobese subjects (r=0.285, p=0.023). In contrast, PCSK9 was not associated positively with TSH in obese subjects (r=-0.249, p=0.49). The relationship of PCSK9 with TSH was different between nonobese and obese subjects when taking age, sex, FT4, and the presence of anti-thyroid antibodies into account (multiple linear regression analysis: β=-0.320, p=0.012 for the interaction term between the presence of obesity and TSH on PCSK9), and was also modified by BMI as a continuous trait (β=-0.241, p=0.062 for the interaction term between BMI and TSH on PCSK9). Non-HDL-C, LDL-C, and apoB levels were dependent on PCSK9 in nonobese subjects (p≤0.01 for each), but not in obese subjects (p>0.50), Accordingly, BMI interacted negatively with PCSK9 on non-HDL-C (p=0.028) and apoB (p=0.071).
  
  
  CONCLUSIONS
  This study suggests that circulating PCSK9 levels correlate with thyroid function even in the normal range. This relationship appears to be blunted by obesity. Thyroid functional status may influence cholesterol metabolism through the PCSK9 pathway.
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Arjan J
authors.initials: AJ
authors.lastname: Kwakernaak
authors.forename: Gilles
authors.initials: G
authors.lastname: Lambert
authors.forename: Anneke C
authors.initials: AC
authors.lastname: Muller Kobold
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
mesh_terms: D050154:Adiposity / Q000502:physiology*; D000328:Adult; D001055:Apolipoproteins B / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000503:physiopathology*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood / Q000502:physiology*; D012697:Serine Endopeptidases / Q000097:blood / Q000502:physiology*; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000097:blood
chemical_list: D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D013972:Thyrotropin; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D013974:Thyroxine