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Iron Status and NAFLD among European Populations: A Bidirectional Two-Sample Mendelian Randomization Study

Background and aim: Previous observational studies have suggested a paradoxical relationship between iron status and the risk of non-alcoholic fatty liver disease (NAFLD). Observed associations in these epidemiological studies fail to show sequential temporality and suffer from problems of confoundi...

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Autores principales: Liu, Cenqin, Chen, Yishu, Zhang, Zhixin, Xie, Jiarong, Yu, Chaohui, Xu, Lei, Li, Youming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9788387/
https://www.ncbi.nlm.nih.gov/pubmed/36558395
http://dx.doi.org/10.3390/nu14245237
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author Liu, Cenqin
Chen, Yishu
Zhang, Zhixin
Xie, Jiarong
Yu, Chaohui
Xu, Lei
Li, Youming
author_facet Liu, Cenqin
Chen, Yishu
Zhang, Zhixin
Xie, Jiarong
Yu, Chaohui
Xu, Lei
Li, Youming
author_sort Liu, Cenqin
collection PubMed
description Background and aim: Previous observational studies have suggested a paradoxical relationship between iron status and the risk of non-alcoholic fatty liver disease (NAFLD). Observed associations in these epidemiological studies fail to show sequential temporality and suffer from problems of confounding. Therefore, we performed a bidirectional two-sample Mendelian randomization (MR) to evaluate the relationship between serum iron status and NAFLD. Methods: The inverse weighted method (IVW) meta-analysis with the fixed-effect model was the main method to estimate the relationship between iron status, including serum ferritin, iron, transferrin saturation (TSAT) and total iron-binding capacity (TIBC), and NAFLD. Weighted median, penalized weighted median, and MR Robust Adjusted Profile Score (MR RAPS) methods were used as additional analyses. Sensitivity analyses were performed with Cochran’s Q test, MR–Egger regression, Steiger filtering, and the MR PRESSO test. Results: Iron status, including serum ferritin, iron, and TSAT, was associated with an increased risk of NAFLD (odds ratio (OR) (95% confidence interval (CI)): 1.25 (1.06, 1.48); 1.24 (1.05, 1.46), 1.16 (1.02, 1.31), respectively). In contrast, minimal effects of NAFLD on serum ferritin, iron, TSAT, and TIBC were observed (OR (95% CI): 1.01 (1.00, 1.02), 1.01 (1.00, 1.02), 1.03 (1.01, 1.05), 1.03 (1.01, 1.05), respectively). Conclusions: Our findings corroborated the causal associations between serum ferritin, iron, TSAT, and NAFLD, which might suggest the potential benefits of iron-related therapy. In addition, NAFLD might, in turn, slightly affect iron homeostasis indicated as serum ferritin, iron, TSAT, and TIBC, but this needs to be further confirmed.
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spelling pubmed-97883872022-12-24 Iron Status and NAFLD among European Populations: A Bidirectional Two-Sample Mendelian Randomization Study Liu, Cenqin Chen, Yishu Zhang, Zhixin Xie, Jiarong Yu, Chaohui Xu, Lei Li, Youming Nutrients Article Background and aim: Previous observational studies have suggested a paradoxical relationship between iron status and the risk of non-alcoholic fatty liver disease (NAFLD). Observed associations in these epidemiological studies fail to show sequential temporality and suffer from problems of confounding. Therefore, we performed a bidirectional two-sample Mendelian randomization (MR) to evaluate the relationship between serum iron status and NAFLD. Methods: The inverse weighted method (IVW) meta-analysis with the fixed-effect model was the main method to estimate the relationship between iron status, including serum ferritin, iron, transferrin saturation (TSAT) and total iron-binding capacity (TIBC), and NAFLD. Weighted median, penalized weighted median, and MR Robust Adjusted Profile Score (MR RAPS) methods were used as additional analyses. Sensitivity analyses were performed with Cochran’s Q test, MR–Egger regression, Steiger filtering, and the MR PRESSO test. Results: Iron status, including serum ferritin, iron, and TSAT, was associated with an increased risk of NAFLD (odds ratio (OR) (95% confidence interval (CI)): 1.25 (1.06, 1.48); 1.24 (1.05, 1.46), 1.16 (1.02, 1.31), respectively). In contrast, minimal effects of NAFLD on serum ferritin, iron, TSAT, and TIBC were observed (OR (95% CI): 1.01 (1.00, 1.02), 1.01 (1.00, 1.02), 1.03 (1.01, 1.05), 1.03 (1.01, 1.05), respectively). Conclusions: Our findings corroborated the causal associations between serum ferritin, iron, TSAT, and NAFLD, which might suggest the potential benefits of iron-related therapy. In addition, NAFLD might, in turn, slightly affect iron homeostasis indicated as serum ferritin, iron, TSAT, and TIBC, but this needs to be further confirmed. MDPI 2022-12-08 /pmc/articles/PMC9788387/ /pubmed/36558395 http://dx.doi.org/10.3390/nu14245237 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Cenqin
Chen, Yishu
Zhang, Zhixin
Xie, Jiarong
Yu, Chaohui
Xu, Lei
Li, Youming
Iron Status and NAFLD among European Populations: A Bidirectional Two-Sample Mendelian Randomization Study
title Iron Status and NAFLD among European Populations: A Bidirectional Two-Sample Mendelian Randomization Study
title_full Iron Status and NAFLD among European Populations: A Bidirectional Two-Sample Mendelian Randomization Study
title_fullStr Iron Status and NAFLD among European Populations: A Bidirectional Two-Sample Mendelian Randomization Study
title_full_unstemmed Iron Status and NAFLD among European Populations: A Bidirectional Two-Sample Mendelian Randomization Study
title_short Iron Status and NAFLD among European Populations: A Bidirectional Two-Sample Mendelian Randomization Study
title_sort iron status and nafld among european populations: a bidirectional two-sample mendelian randomization study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9788387/
https://www.ncbi.nlm.nih.gov/pubmed/36558395
http://dx.doi.org/10.3390/nu14245237
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