Department of Hepatobiliary and Pancreatic Surgery II, General Surgery Center, The First Hospital of Jilin University, Changchun, China.
Front Endocrinol (Lausanne). 2023 Mar 29;14:1166740. doi: 10.3389/fendo.2023.1166740. eCollection 2023.
To investigate the relationship between function of thyroid, lipids, and cholelithiasis and to identify whether lipids mediate the causal relationship between function of thyroid and cholelithiasis.
A Mendelian randomization (MR) study of two samples was performed to determine the association of thyroid function with cholelithiasis. A two-step MR was also performed to identify whether lipid metabolism traits mediate the effects of thyroid function on cholelithiasis. A method of inverse variance weighted (IVW), weighted median method, maximum likelihood, MR-Egger, MR-robust adjusted profile score (MR-RAPS) method, and MR pleiotropy residual sum and outlier test (MR-PRESSO) methods were utilized to obtain MR estimates.
The IVW method revealed that FT4 levels were correlated with an elevated risk of cholelithiasis (OR: 1.149, 95% CI: 1.082-1.283, = 0.014). Apolipoprotein B (OR: 1.255, 95% CI: 1.027-1.535, = 0.027) and low-density lipoprotein cholesterol (LDL-C) (OR: 1.354, 95% CI: 1.060-1.731, = 0.016) were also correlated with an elevated risk of cholelithiasis. The IVW method demonstrated that FT4 levels were correlated with the elevated risk of apolipoprotein B (OR: 1.087, 95% CI: 1.019-1.159, = 0.015) and LDL-C (OR: 1.084, 95% CI: 1.018-1.153, = 0.012). Thyroid function and the risk of cholelithiasis are mediated by LDL-C and apolipoprotein B. LDL-C and apolipoprotein B had 17.4% and 13.5% of the mediatory effects, respectively.
We demonstrated that FT4, LDL-C, and apolipoprotein B had significant causal effects on cholelithiasis, with evidence that LDL-C and apolipoprotein B mediated the effects of FT4 on cholelithiasis risk. Patients with high FT4 levels should be given special attention because they may delay or limit the long-term impact on cholelithiasis risk.
探讨甲状腺功能、血脂与胆石病的关系，明确血脂是否介导甲状腺功能与胆石病之间的因果关系。
本研究采用孟德尔随机化（Mendelian randomization，MR）分析两个样本，以确定甲状腺功能与胆石病之间的关联。采用两步 MR 分析以确定脂质代谢特征是否介导甲状腺功能对胆石病的影响。采用逆方差加权（inverse variance weighted，IVW）、加权中位数法、最大似然法、MR-Egger 法、MR-稳健调整的 Profile 得分（MR-robust adjusted Profile score，MR-RAPS）法和 MR 偏倚残差和异常值检验（MR pleiotropy residual sum and outlier test，MR-PRESSO）法获得 MR 估计值。
IVW 方法显示，游离甲状腺素（free thyroxine，FT4）水平与胆石病风险升高相关（比值比：1.149，95%置信区间：1.082-1.283， = 0.014）。载脂蛋白 B（apolipoprotein B，ApoB）（比值比：1.255，95%置信区间：1.027-1.535， = 0.027）和低密度脂蛋白胆固醇（low-density lipoprotein cholesterol，LDL-C）（比值比：1.354，95%置信区间：1.060-1.731， = 0.016）也与胆石病风险升高相关。IVW 方法显示，FT4 水平与 ApoB（比值比：1.087，95%置信区间：1.019-1.159， = 0.015）和 LDL-C（比值比：1.084，95%置信区间：1.018-1.153， = 0.012）风险升高相关。甲状腺功能与胆石病的发生之间存在因果关系，其部分机制是通过 LDL-C 和 ApoB 介导的。LDL-C 和 ApoB 的中介效应分别为 17.4%和 13.5%。
本研究表明，FT4、LDL-C 和 ApoB 对胆石病具有显著的因果作用，并且 LDL-C 和 ApoB 介导了 FT4 对胆石病风险的影响。FT4 水平较高的患者应引起特别关注，因为这可能会延迟或限制其对胆石病风险的长期影响。
