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Ethnic differences in ApoC-III concentration and the risk of cardiovascular disease: No evidence for the cardioprotective role of rare/loss of function APOC3 variants in non-Europeans
BACKGROUND: Hypertriglyceridemia is as an independent risk factor for cardiovascular disease (CVD). Apolipoprotein C-III (ApoC-III) is known to regulate triglyceride (TG) metabolism. However, the causal association between ApoC-III and CVD development is unclear. The objectives were to examine the i...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9075110/ https://www.ncbi.nlm.nih.gov/pubmed/35528316 http://dx.doi.org/10.1016/j.ahjo.2022.100128 |
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author | Rout, Madhusmita Lerner, Megan Blackett, Piers R. Peyton, Marvin D. Stavrakis, Stavros Sidorov, Evgeny Sanghera, Dharambir K. |
author_facet | Rout, Madhusmita Lerner, Megan Blackett, Piers R. Peyton, Marvin D. Stavrakis, Stavros Sidorov, Evgeny Sanghera, Dharambir K. |
author_sort | Rout, Madhusmita |
collection | PubMed |
description | BACKGROUND: Hypertriglyceridemia is as an independent risk factor for cardiovascular disease (CVD). Apolipoprotein C-III (ApoC-III) is known to regulate triglyceride (TG) metabolism. However, the causal association between ApoC-III and CVD development is unclear. The objectives were to examine the impact of ApoC-III concentration on TG and lipoproteins and investigate the role of known rare loss-of-function APOC3 variants for modulating ApoC-III, TG concentrations and CVD risk in different ethnic groups. METHODS: Plasma ApoC-III levels were measured in a multiethnic sample of 518 individuals comprising 271 Asian Indians (Sikhs), 87 Caucasians, 80 African Americans, and 80 Hispanics. RESULTS: ApoC-III levels showed a robust association with TG in Asian Indians (r = 0.5, p = 1.1 × 10(−23)), Caucasians (r = 0.4, p = 7.2 × 10(−4)), and Hispanics (r = 0.9, p = 2.7x × 10(−28)). African Americans had lowest ApoC-III and TG concentrations and highest (44%) prevalence of coronary artery disease (CAD). ApoC-III levels correlated with fasting blood glucose (r = 0.25, p = 6.1 × 10(−5)) in Asian Indians and central adiposity in Hispanics (waist: r = 0.22, p = 0.05; waist-hip ratio: r = 0.24, p = 0.04). The carriers of rare variants IVS1-2G-A (rs373975305); A43T (rs147210663) and IVS3 + 1G-T (rs140621530) showed high TG but not low ApoC-III levels in Asian Indians and Caucasians. CONCLUSION: These results highlight the challenges of generalizing antisense ApoC-III inhibition for treating atherosclerotic disease in dyslipidemia that may benefit only specific sub-populations. The observed ethnic differences in ApoC-III concentrations and CAD risk factors, emphasize in-depth genetic and metabolomics evaluations on diverse ancestries. |
format | Online Article Text |
id | pubmed-9075110 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
record_format | MEDLINE/PubMed |
spelling | pubmed-90751102022-05-06 Ethnic differences in ApoC-III concentration and the risk of cardiovascular disease: No evidence for the cardioprotective role of rare/loss of function APOC3 variants in non-Europeans Rout, Madhusmita Lerner, Megan Blackett, Piers R. Peyton, Marvin D. Stavrakis, Stavros Sidorov, Evgeny Sanghera, Dharambir K. Am Heart J Plus Article BACKGROUND: Hypertriglyceridemia is as an independent risk factor for cardiovascular disease (CVD). Apolipoprotein C-III (ApoC-III) is known to regulate triglyceride (TG) metabolism. However, the causal association between ApoC-III and CVD development is unclear. The objectives were to examine the impact of ApoC-III concentration on TG and lipoproteins and investigate the role of known rare loss-of-function APOC3 variants for modulating ApoC-III, TG concentrations and CVD risk in different ethnic groups. METHODS: Plasma ApoC-III levels were measured in a multiethnic sample of 518 individuals comprising 271 Asian Indians (Sikhs), 87 Caucasians, 80 African Americans, and 80 Hispanics. RESULTS: ApoC-III levels showed a robust association with TG in Asian Indians (r = 0.5, p = 1.1 × 10(−23)), Caucasians (r = 0.4, p = 7.2 × 10(−4)), and Hispanics (r = 0.9, p = 2.7x × 10(−28)). African Americans had lowest ApoC-III and TG concentrations and highest (44%) prevalence of coronary artery disease (CAD). ApoC-III levels correlated with fasting blood glucose (r = 0.25, p = 6.1 × 10(−5)) in Asian Indians and central adiposity in Hispanics (waist: r = 0.22, p = 0.05; waist-hip ratio: r = 0.24, p = 0.04). The carriers of rare variants IVS1-2G-A (rs373975305); A43T (rs147210663) and IVS3 + 1G-T (rs140621530) showed high TG but not low ApoC-III levels in Asian Indians and Caucasians. CONCLUSION: These results highlight the challenges of generalizing antisense ApoC-III inhibition for treating atherosclerotic disease in dyslipidemia that may benefit only specific sub-populations. The observed ethnic differences in ApoC-III concentrations and CAD risk factors, emphasize in-depth genetic and metabolomics evaluations on diverse ancestries. 2022-01 2022-03-31 /pmc/articles/PMC9075110/ /pubmed/35528316 http://dx.doi.org/10.1016/j.ahjo.2022.100128 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Rout, Madhusmita Lerner, Megan Blackett, Piers R. Peyton, Marvin D. Stavrakis, Stavros Sidorov, Evgeny Sanghera, Dharambir K. Ethnic differences in ApoC-III concentration and the risk of cardiovascular disease: No evidence for the cardioprotective role of rare/loss of function APOC3 variants in non-Europeans |
title | Ethnic differences in ApoC-III concentration and the risk of cardiovascular disease: No evidence for the cardioprotective role of rare/loss of function APOC3 variants in non-Europeans |
title_full | Ethnic differences in ApoC-III concentration and the risk of cardiovascular disease: No evidence for the cardioprotective role of rare/loss of function APOC3 variants in non-Europeans |
title_fullStr | Ethnic differences in ApoC-III concentration and the risk of cardiovascular disease: No evidence for the cardioprotective role of rare/loss of function APOC3 variants in non-Europeans |
title_full_unstemmed | Ethnic differences in ApoC-III concentration and the risk of cardiovascular disease: No evidence for the cardioprotective role of rare/loss of function APOC3 variants in non-Europeans |
title_short | Ethnic differences in ApoC-III concentration and the risk of cardiovascular disease: No evidence for the cardioprotective role of rare/loss of function APOC3 variants in non-Europeans |
title_sort | ethnic differences in apoc-iii concentration and the risk of cardiovascular disease: no evidence for the cardioprotective role of rare/loss of function apoc3 variants in non-europeans |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9075110/ https://www.ncbi.nlm.nih.gov/pubmed/35528316 http://dx.doi.org/10.1016/j.ahjo.2022.100128 |
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