Novel Insights into Causal Effects of Lipid and Lipid-Lowering Targets with Autoimmune Thyroid Disease: A Mendelian Randomization Study.

IF 6.2 Q1 IMMUNOLOGY

ImmunoTargets and Therapy Pub Date : 2024-11-23 eCollection Date: 2024-01-01 DOI:10.2147/ITT.S487319

Chang Su, Juan Tian, Xueqing He, Xiaona Chang, Guang Wang, Jia Liu

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引用次数: 0

Abstract

Background: Dyslipidemia has been implicated in the pathogenesis of several diseases, including thyroid dysfunction and immune disorders. However, whether circulating lipids and long-term use of lipid-lowering drugs influence the development of autoimmune thyroid disease (AITD) remains unclear. This study aims to evaluate the effects of lipid-lowering drugs on AITD and explore their potential mechanisms.

Methods: Two-sample and two-step Mendelian randomization (MR) studies were performed to assess the causal relationships between circulating lipids (LDL-C, TC, TG, and ApoB) and seven lipid-lowering drug targets (ApoB, CETP, HMGCR, LDLR, NPC1L1, PCSK9, and PPARα) with AITD. Mediation analyses were conducted to explore potential mediating factors.

Results: There was no clear causality between circulating lipids (ApoB, LDL-C, TC, and TG) and AITD (p > 0.05). ApoB inhibition is related to a reduced risk of autoimmune thyroiditis (AT) (OR = 0.462, p= 0.046), while PCSK9 inhibition is related to reduced Graves' disease (GD) risk (OR = 0. 551, p = 0.033). Moreover, PCSK9 inhibition (OR = 0.735, p = 0.003), LDLR inhibition (OR = 0.779, p = 0.027), and NPC1L1 inhibition (OR = 0.599, p = 0.016) reduced the risk of autoimmune hypothyroidism (AIH). Mediation analysis showed that NPC1L1 inhibition and PCSK9 inhibition exerted effects on AIH through IL-4 and FGF-19 levels. And the effect of PCSK9 inhibition on GD through TNF-β levels.

Conclusion: There was no clear causality between circulating lipids (ApoB, LDL-C, TC, and TG) and AITD. Lipid-lowering drug target gene inhibitors reduced the AITD risk by modulating inflammatory factors.

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关于自身免疫性甲状腺疾病的血脂和降脂靶点因果效应的新见解：孟德尔随机化研究

背景：血脂异常与多种疾病的发病机制有关，包括甲状腺功能障碍和免疫紊乱。然而，循环血脂和长期服用降脂药是否会影响自身免疫性甲状腺疾病（AITD）的发生仍不清楚。本研究旨在评估降脂药对自身免疫性甲状腺疾病的影响，并探索其潜在机制：方法：研究人员进行了双样本和两步孟德尔随机化（MR）研究，以评估循环血脂（LDL-C、TC、TG和载脂蛋白B）和七个降脂药物靶点（载脂蛋白B、CETP、HMGCR、LDLR、NPC1L1、PCSK9和PPARα）与AITD之间的因果关系。研究人员进行了中介分析，以探索潜在的中介因素：结果：循环血脂（载脂蛋白B、低密度脂蛋白胆固醇、总胆固醇和总胆固醇）与 AITD 之间没有明显的因果关系（P > 0.05）。载脂蛋白B抑制与自身免疫性甲状腺炎（AT）风险降低有关（OR=0.462，P= 0.046），而PCSK9抑制与巴塞杜氏病（GD）风险降低有关（OR=0.551，P= 0.033）。此外，PCSK9抑制（OR = 0.735，p = 0.003）、LDLR抑制（OR = 0.779，p = 0.027）和NPC1L1抑制（OR = 0.599，p = 0.016）降低了自身免疫性甲状腺功能减退症（AIH）的风险。中介分析显示，NPC1L1抑制和PCSK9抑制通过IL-4和FGF-19水平对AIH产生影响。结论：NPC1L1抑制和PCSK9抑制通过IL-4和FGF-19水平对AIH产生影响，而PCSK9抑制通过TNF-β水平对GD产生影响：结论：循环血脂（载脂蛋白B、低密度脂蛋白胆固醇、总胆固醇和总胆固醇）与AITD之间没有明确的因果关系。降脂药物靶基因抑制剂通过调节炎症因子降低了 AITD 风险。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ImmunoTargets and Therapy IMMUNOLOGY-

CiteScore

16.50

自引率

0.00%

发文量

审稿时长

16 weeks

期刊介绍： Immuno Targets and Therapy is an international, peer-reviewed open access journal focusing on the immunological basis of diseases, potential targets for immune based therapy and treatment protocols employed to improve patient management. Basic immunology and physiology of the immune system in health, and disease will be also covered.In addition, the journal will focus on the impact of management programs and new therapeutic agents and protocols on patient perspectives such as quality of life, adherence and satisfaction.