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. 2022 Jan:13:100128.
doi: 10.1016/j.ahjo.2022.100128. Epub 2022 Mar 31.

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

Madhusmita Rout  1 , Megan Lerner  2 , Piers R Blackett  1 , Marvin D Peyton  2 , Stavros Stavrakis  3 , Evgeny Sidorov  4 , Dharambir K Sanghera  1   5   6   7   8
Affiliations

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

Madhusmita Rout et al. Am Heart J Plus. 2022 Jan.

Abstract

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.

Keywords: Apolipoprotein C-III concentration; Cardiovascular disease; Circulating triglycerides; Ethnicity; Lipid metabolites; Rare variants.

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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
Distribution of mean levels of TG and ApoC-III concentrations (mg/dL) in different Ethnic groups. ApoC-III = Apolipoprotein C-III; TG = triglycerides.
Fig. 2
Fig. 2
Scatter plot showing the correlation between the distribution of ApoC-III concentration (X-axis) vs.TG levels (Y-axis) among different ethnic groups. ApoC-III = Apolipoprotein C-III; TG = triglycerides.
Fig. 3
Fig. 3
Distribution of overall mean levels of TG and ApoC-III concentrations (mg/dL) among carriers and non-carriers of earlier known APOC3 loss-of-function (LoF) rare variants (IVS1-2G-A (rs373975305); IVS2 + 1G-A (rs138326449), IVS3 + 1G-T (rs140621530) and A43T (rs147210663)) in different ethnic groups. ApoC-III = Apolipoprotein C-III; TG = triglycerides; N = number of individuals.
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