Please use this identifier to cite or link to this item:
Title: APOC3 genetic variation, serum triglycerides, and risk of coronary artery disease in Asian Indians, Europeans, and other ethnic groups
Authors: Goyal, Shiwali
Tanigawa, Yosuke
Zhang, Weihua
Chai, Jin-Fang
Almeida, Marcio
Sim, Xueling
Lerner, Megan
Chainakul, Juliane
Ramiu, Jonathan Garcia
Seraphin, Chanel
Apple, Blair
Vaughan, April
Muniu, James
Peralta, Juan
Lehman, Donna M.
Ralhan, Sarju
Wander, Gurpreet S.
Singh, Jai Rup
Mehra, Narinder K.
Sidorov, Evgeny
Peyton, Marvin D.
Blackett, Piers R.
Curran, Joanne E.
Tai, E Shyong
van Dam, Rob
Cheng, Ching-Yu
Duggirala, Ravindranath
Blangero, John
Chambers, John Campbell
Sabanayagam, Charumathi
Kooner, Jaspal S.
Rivas, Manuel A.
Aston, Christopher E.
Sanghera, Dharambir K.
Keywords: Science::Medicine
Issue Date: 2021
Source: Goyal, S., Tanigawa, Y., Zhang, W., Chai, J., Almeida, M., Sim, X., Lerner, M., Chainakul, J., Ramiu, J. G., Seraphin, C., Apple, B., Vaughan, A., Muniu, J., Peralta, J., Lehman, D. M., Ralhan, S., Wander, G. S., Singh, J. R., Mehra, N. K., ...Sanghera, D. K. (2021). APOC3 genetic variation, serum triglycerides, and risk of coronary artery disease in Asian Indians, Europeans, and other ethnic groups. Lipids in Health and Disease, 20(1), 113-.
Project: NMRC/ STaR/0028/2017 
Journal: Lipids in Health and Disease 
Abstract: Background: Hypertriglyceridemia has emerged as a critical coronary artery disease (CAD) risk factor. Rare loss-of function (LoF) variants in apolipoprotein C-III have been reported to reduce triglycerides (TG) and are cardioprotective in American Indians and Europeans. However, there is a lack of data in other Europeans and non-Europeans. Also, whether genetically increased plasma TG due to ApoC-III is causally associated with increased CAD risk is still unclear and inconsistent. The objectives of this study were to verify the cardioprotective role of earlier reported six LoF variants of APOC3 in South Asians and other multi-ethnic cohorts and to evaluate the causal association of TG raising common variants for increasing CAD risk. Methods: We performed gene-centric and Mendelian randomization analyses and evaluated the role of genetic variation encompassing APOC3 for affecting circulating TG and the risk for developing CAD. Results: One rare LoF variant (rs138326449) with a 37% reduction in TG was associated with lowered risk for CAD in Europeans (p = 0.007), but we could not confirm this association in Asian Indians (p = 0.641). Our data could not validate the cardioprotective role of other five LoF variants analysed. A common variant rs5128 in the APOC3 was strongly associated with elevated TG levels showing a p-value 2.8 × 10− 424. Measures of plasma ApoC-III in a small subset of Sikhs revealed a 37% increase in ApoC-III concentrations among homozygous mutant carriers than the wild-type carriers of rs5128. A genetically instrumented per 1SD increment of plasma TG level of 15 mg/dL would cause a mild increase (3%) in the risk for CAD (p = 0.042). Conclusions: Our results highlight the challenges of inclusion of rare variant information in clinical risk assessment and the generalizability of implementation of ApoC-III inhibition for treating atherosclerotic disease. More studies would be needed to confirm whether genetically raised TG and ApoC-III concentrations would increase CAD risk.
ISSN: 1476-511X
DOI: 10.1186/s12944-021-01531-8
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Rights: © 2021 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

Files in This Item:
File Description SizeFormat 
s12944-021-01531-8.pdf1.58 MBAdobe PDFThumbnail

Citations 50

Updated on Nov 26, 2023

Web of ScienceTM
Citations 20

Updated on Oct 25, 2023

Page view(s)

Updated on Nov 29, 2023


Updated on Nov 29, 2023

Google ScholarTM




Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.