Key result
Plasma ApoC-III levels strongly correlate with triglycerides across diverse ethnic groups despite rare APOC3 variants.
Observational (n=518)
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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. 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. 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. 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.
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Rout et al. (2022) conducted an observational in Dyslipidemia and cardiovascular disease (n=518). Plasma ApoC-III concentration and rare loss-of-function APOC3 variants vs. Different ethnic groups and non-carriers was evaluated on Association of ApoC-III concentration and APOC3 variants with triglyceride levels and coronary artery disease risk (r = 0.5 (Asian Indians), r = 0.4 (Caucasians), r = 0.9 (Hispanics), p=1.1 × 10−23 (Asian Indians), 7.2 × 10−4 (Caucasians), 2.7 × 10−28 (Hispanics)). Plasma ApoC-III levels strongly correlated with triglycerides in Asian Indians (r=0.5), Caucasians (r=0.4), and Hispanics (r=0.9), while rare APOC3 variants did not lower ApoC-III.
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