دورية أكاديمية
أعرض في EDS

The relationship between genetic liver fat and coronary heart disease is explained by apoB-containing lipoproteins.

التفاصيل البيبلوغرافية
العنوان: The relationship between genetic liver fat and coronary heart disease is explained by apoB-containing lipoproteins.
المؤلفون: Björnson E; Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden. Electronic address: elias.bjornson@wlab.gu.se., Adiels M; Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden; School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden., Bergström G; Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Physiology, 413 45, Gothenburg, Sweden., Gummesson A; Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Genetics, 413 45, Gothenburg, Sweden.
المصدر: Atherosclerosis [Atherosclerosis] 2024 Jan; Vol. 388, pp. 117397. Date of Electronic Publication: 2023 Nov 29.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Ireland NLM ID: 0242543 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-1484 (Electronic) Linking ISSN: 00219150 NLM ISO Abbreviation: Atherosclerosis Subsets: MEDLINE
أسماء مطبوعة: Publication: Limerick : Elsevier
Original Publication: Amsterdam, Elsevier.
مواضيع طبية MeSH: Coronary Disease*/diagnosis , Coronary Disease*/epidemiology , Coronary Disease*/genetics , Genome-Wide Association Study*, Humans ; Apolipoproteins B/genetics ; Cholesterol, LDL/genetics ; Lipoproteins/genetics ; Liver ; Mendelian Randomization Analysis
مستخلص: Background: The relationship between genetically-driven liver fat and coronary heart disease (CHD) remains unclear. ApoB-containing lipoproteins are known causal factors for CHD and may explain this relationship.
Methods and Results: We conducted a genome-wide association study (GWAS) in the UK Biobank to identify genetic variants associated with liver fat. We then investigated the effects that these genetic variants had on both apoB-containing lipoproteins and CHD. Using Mendelian Randomization (MR) analyses, we examined if the relationship between genetically-driven liver fat and CHD could be attributed to its effect on apoB-containing lipoproteins. We found 25 independent liver-fat associated single-nucleotide polymorphisms (SNPs) with differing effects on lipoprotein metabolism. The SNPs were classified into three groups/clusters. The first cluster (N = 3 SNPs) displayed lipoprotein-raising effects. The second cluster (N = 12 SNPs) displayed neutral effects on lipoproteins and the third cluster (N = 10 SNPs) displayed lipoprotein-lowering effects. For every 1% higher liver fat, the first cluster showed an increased risk of CHD (OR = 1.157 [95% CI: 1.108-1.208]). The second cluster showed a non-significant effect on CHD (OR = 0.988 [95% CI: 0.965-1.012], whereas the third cluster showed a protective effect of increased liver fat on CHD (OR = 0.942 [95% CI: 0.897-0.989]). When adjusting for apoB, the risk for CHD became null.
Conclusions: Here, we identify 25 liver-fat associated SNPs. We find that SNPs that increase, decrease or have neutral effects on apoB-containing lipoproteins show increased, decreased or neutral effects on CHD, respectively. Therefore, the relationship between genetically-driven liver fat and CHD is mediated by the causal effect of apoB.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
التعليقات: Comment in: Atherosclerosis. 2024 Jan;388:117410. (PMID: 38092624)
فهرسة مساهمة: Keywords: Apolipoprotein-B (apoB); Coronary heart disease (CHD); Mendelian randomization (MR); Non-alcoholic fatty liver disease (NAFLD); Single-nucleotide polymorphisms (SNPs)
المشرفين على المادة: 0 (Apolipoproteins B)
0 (Cholesterol, LDL)
0 (Lipoproteins)
0 (APOB protein, human)
تواريخ الأحداث: Date Created: 20231215 Date Completed: 20240127 Latest Revision: 20240215
رمز التحديث: 20240215
DOI: 10.1016/j.atherosclerosis.2023.117397
PMID: 38102060
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-1484
DOI:10.1016/j.atherosclerosis.2023.117397