Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Thyroid. 2013 Feb;23(2):166-72. doi: 10.1089/thy.2012.0434.
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.
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)).
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).
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.
甲状腺功能状态对脂蛋白代谢的影响可能会延伸到甲状腺功能正常范围内。载脂蛋白 B (apoB)、非高密度脂蛋白胆固醇 (non-HDL-C)、低密度脂蛋白胆固醇 (LDL-C)、前蛋白转化酶枯草溶菌素 9 (PCSK9)。PCSK9 下调 LDL 受体的表达，导致 LDL 胆固醇 (LDL-C) 升高。在这里，我们测试了在非肥胖和肥胖的甲状腺功能正常的受试者中，血浆 PCSK9 是否与甲状腺功能相关。
我们评估了在 74 名甲状腺功能正常的受试者（31 名女性；TSH 在 0.5 到 4.0 mU/L 之间，游离甲状腺素 [FT4] 在 11.0 到 19.5 pM 之间）中，TSH 对 PCSK9 的影响程度，这些受试者的肥胖程度不同（体重指数 [BMI] 从 20.2 到 40.4 kg/m2）。
在 64 名非肥胖受试者（BMI<30 kg/m2）和 10 名肥胖受试者（BMI≥30 kg/m2）之间，TSH、FT4、PCSK9、非高密度脂蛋白胆固醇（non-HDL-C）、LDL-C 和载脂蛋白 B（apoB）水平没有差异（p>0.20）。在非肥胖受试者中，PCSK9 与 TSH 呈正相关（r=0.285，p=0.023）。相反，在肥胖受试者中，PCSK9 与 TSH 无正相关（r=-0.249，p=0.49）。当考虑年龄、性别、FT4 和抗甲状腺抗体的存在时，PCSK9 与 TSH 的关系在非肥胖和肥胖受试者之间是不同的（多元线性回归分析：β=-0.320，p=0.012，肥胖和 TSH 对 PCSK9 的交互项），并且还受 BMI 作为连续特征的影响（β=-0.241，p=0.062，BMI 和 TSH 对 PCSK9 的交互项）。在非肥胖受试者中，非-HDL-C、LDL-C 和 apoB 水平依赖于 PCSK9（p≤0.01），但在肥胖受试者中则不依赖（p>0.50），相应地，BMI 与 PCSK9 对非-HDL-C（p=0.028）和 apoB（p=0.071）的交互作用呈负相关。
本研究表明，即使在甲状腺功能正常范围内，循环 PCSK9 水平也与甲状腺功能相关。这种关系似乎被肥胖所削弱。甲状腺功能状态可能通过 PCSK9 途径影响胆固醇代谢。
