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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 C.
Sabanayagam, Charumathi 
Kooner, Jaspal S.
Rivas, Manuel A.
Aston, Christopher E.
Sanghera, Dharambir K.
Keywords: ApoC-III
Asian Indians
Coronary artery disease risk
Mendelian randomization
Rare and common variants
Issue Date: 21-Sep-2021
Publisher: BioMed Central Ltd
Citation: 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 C., Sabanayagam, Charumathi, Kooner, Jaspal S., Rivas, Manuel A., Aston, Christopher E., Sanghera, Dharambir K. (2021-09-21). 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. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
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. © 2021, The Author(s).
Source Title: Lipids in Health and Disease
ISSN: 1476-511X
DOI: 10.1186/s12944-021-01531-8
Rights: Attribution 4.0 International
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