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

• Published in: American heart journal plus Vol. 13; p. 100128
• Main Authors: Rout, Madhusmita, Lerner, Megan, Blackett, Piers R., Peyton, Marvin D., Stavrakis, Stavros, Sidorov, Evgeny, Sanghera, Dharambir K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2022; Elsevier
• Subjects: Apolipoprotein C-III concentration; Cardiovascular disease; Circulating triglycerides; Ethnicity; Lipid metabolites; Rare variants; TRLs; LoF; GWAS; Apolipoprotein C-III concentration; Rare variants; CAD; T2D; Cardiovascular disease; ApoC-III; CVD; Circulating triglycerides; Ethnicity; TG; Lipid metabolites
• ISSN: 2666-6022; 2666-6022
• DOI: 10.1016/j.ahjo.2022.100128

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.