Novel Insights into Causal Effects of Lipid and Lipid-Lowering Targets with Autoimmune Thyroid Disease: A Mendelian Randomization Study
Chang Su, Juan Tian, Xueqing He, Xiaona Chang, Guang Wang, Jia Liu Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of ChinaCorrespondence: Guang Wang; Jia Liu, Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Med...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2024-11-01
|
| Series: | ImmunoTargets and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/novel-insights-into-causal-effects-of-lipid-and-lipid-lowering-targets-peer-reviewed-fulltext-article-ITT |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846158080340918272 |
|---|---|
| author | Su C Tian J He X Chang X Wang G Liu J |
| author_facet | Su C Tian J He X Chang X Wang G Liu J |
| author_sort | Su C |
| collection | DOAJ |
| description | Chang Su, Juan Tian, Xueqing He, Xiaona Chang, Guang Wang, Jia Liu Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of ChinaCorrespondence: Guang Wang; Jia Liu, Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, NO. 8, Gongti South Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +8610-85231737 ; +8610-85231710, Email drwg6688@126.com; liujia0116@126.comBackground: 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.Keywords: Mendelian randomization, drug targeting, thyroid autoimmune disease, lipid trait, inflammatory factors |
| format | Article |
| id | doaj-art-1b43e19269b5493d9d7b2e2fb6df4940 |
| institution | Kabale University |
| issn | 2253-1556 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | ImmunoTargets and Therapy |
| spelling | doaj-art-1b43e19269b5493d9d7b2e2fb6df49402024-11-24T16:45:57ZengDove Medical PressImmunoTargets and Therapy2253-15562024-11-01Volume 1363164197614Novel Insights into Causal Effects of Lipid and Lipid-Lowering Targets with Autoimmune Thyroid Disease: A Mendelian Randomization StudySu CTian JHe XChang XWang GLiu JChang Su, Juan Tian, Xueqing He, Xiaona Chang, Guang Wang, Jia Liu Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of ChinaCorrespondence: Guang Wang; Jia Liu, Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, NO. 8, Gongti South Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +8610-85231737 ; +8610-85231710, Email drwg6688@126.com; liujia0116@126.comBackground: 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.Keywords: Mendelian randomization, drug targeting, thyroid autoimmune disease, lipid trait, inflammatory factorshttps://www.dovepress.com/novel-insights-into-causal-effects-of-lipid-and-lipid-lowering-targets-peer-reviewed-fulltext-article-ITTmendelian randomizationdrug targetingthyroid autoimmune diseaselipid traitinflammatory factors |
| spellingShingle | Su C Tian J He X Chang X Wang G Liu J Novel Insights into Causal Effects of Lipid and Lipid-Lowering Targets with Autoimmune Thyroid Disease: A Mendelian Randomization Study ImmunoTargets and Therapy mendelian randomization drug targeting thyroid autoimmune disease lipid trait inflammatory factors |
| title | Novel Insights into Causal Effects of Lipid and Lipid-Lowering Targets with Autoimmune Thyroid Disease: A Mendelian Randomization Study |
| title_full | Novel Insights into Causal Effects of Lipid and Lipid-Lowering Targets with Autoimmune Thyroid Disease: A Mendelian Randomization Study |
| title_fullStr | Novel Insights into Causal Effects of Lipid and Lipid-Lowering Targets with Autoimmune Thyroid Disease: A Mendelian Randomization Study |
| title_full_unstemmed | Novel Insights into Causal Effects of Lipid and Lipid-Lowering Targets with Autoimmune Thyroid Disease: A Mendelian Randomization Study |
| title_short | Novel Insights into Causal Effects of Lipid and Lipid-Lowering Targets with Autoimmune Thyroid Disease: A Mendelian Randomization Study |
| title_sort | novel insights into causal effects of lipid and lipid lowering targets with autoimmune thyroid disease a mendelian randomization study |
| topic | mendelian randomization drug targeting thyroid autoimmune disease lipid trait inflammatory factors |
| url | https://www.dovepress.com/novel-insights-into-causal-effects-of-lipid-and-lipid-lowering-targets-peer-reviewed-fulltext-article-ITT |
| work_keys_str_mv | AT suc novelinsightsintocausaleffectsoflipidandlipidloweringtargetswithautoimmunethyroiddiseaseamendelianrandomizationstudy AT tianj novelinsightsintocausaleffectsoflipidandlipidloweringtargetswithautoimmunethyroiddiseaseamendelianrandomizationstudy AT hex novelinsightsintocausaleffectsoflipidandlipidloweringtargetswithautoimmunethyroiddiseaseamendelianrandomizationstudy AT changx novelinsightsintocausaleffectsoflipidandlipidloweringtargetswithautoimmunethyroiddiseaseamendelianrandomizationstudy AT wangg novelinsightsintocausaleffectsoflipidandlipidloweringtargetswithautoimmunethyroiddiseaseamendelianrandomizationstudy AT liuj novelinsightsintocausaleffectsoflipidandlipidloweringtargetswithautoimmunethyroiddiseaseamendelianrandomizationstudy |