Dataset Information

APOC3 genetic variation, serum triglycerides, and risk of coronary artery disease in Asian Indians, Europeans, and other ethnic groups.

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.

SUBMITTER: Goyal S

PROVIDER: S-EPMC8456544 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

APOC3 genetic variation, serum triglycerides, and risk of coronary artery disease in Asian Indians, Europeans, and other ethnic groups.

Goyal Shiwali S Tanigawa Yosuke Y Zhang Weihua W Chai Jin-Fang JF Almeida Marcio M Sim Xueling X Lerner Megan M Chainakul Juliane J Ramiu Jonathan Garcia JG Seraphin Chanel C Apple Blair B Vaughan April A Muniu James J Peralta Juan J Lehman Donna M DM Ralhan Sarju S Wander Gurpreet S GS Singh Jai Rup JR Mehra Narinder K NK Sidorov Evgeny E Peyton Marvin D MD Blackett Piers R PR Curran Joanne E JE Tai E Shyong ES van Dam Rob R Cheng Ching-Yu CY Duggirala Ravindranath R Blangero John J Chambers John C JC Sabanayagam Charumathi C Kooner Jaspal S JS Rivas Manuel A MA Aston Christopher E CE Sanghera Dharambir K DK

Lipids in health and disease 20210921 1

<h4>Background</h4>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 obj ...[more]

PMID: 34548093

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Project description:PurposeTo determine the incidence and prevalence of different glaucoma types among Asian Americans and other races, and evaluate the hazard for glaucoma among different races and Asian ethnicities.DesignRetrospective, longitudinal, cohort study.ParticipantsA group of 2,259,061 eye care recipients, aged ? 40, who were enrolled in a US managed-care network in 2001-2007.MethodsIncidence and prevalence rates of open-angle glaucoma (OAG), narrow-angle glaucoma (NAG), and normal-tension glaucoma (NTG) were calculated and stratified by race and Asian ethnicity. Cox regression was performed to assess the hazard of developing OAG, NAG, and NTG for Asian Americans and other races, and among different Asian ethnicities, with adjustment for potentially confounding variables.Main outcome measuresMultivariable adjusted hazard of OAG, NAG, and NTG among different races and Asian ethnicities.ResultsThe OAG prevalence rate for Asian Americans, 6.52%, was similar to that of Latinos (6.40%) and higher than that of non-Hispanic whites (5.59%). The NAG and NTG prevalence rates were considerably higher among Asian Americans (3.01% and 0.73%, respectively) relative to other races. After adjustment for potential confounding factors, Asian Americans had a 51% increased hazard of OAG (adjusted hazard ratio [HR], 1.51 [95% confidence interval (CI), 1.42-1.60]), a 123% increased hazard of NAG (adjusted HR, 2.23; CI, 2.07-2.41), and a 159% increased hazard of NTG (adjusted HR, 2.59; CI, 2.22-3.02) compared with non-Hispanic whites. Vietnamese Americans (adjusted HR, 3.78; CI, 3.19-4.48), Pakistani Americans (adjusted HR, 2.45, CI 1.50-4.01), and Chinese Americans (adjusted HR, 2.31, CI 2.06-2.59) had considerably higher hazards of NAG, whereas Japanese Americans (adjusted HR, 4.37, CI 3.24-5.89) had a substantially higher hazard of NTG, compared with non-Asian Americans.ConclusionsGiven the rapid rise in the number of Asian Americans in the US population, resources should be devoted to identifying and treating glaucoma in these patients. Eye-care providers should be aware of the increased risk for OAG, NAG, and NTG among Asian Americans relative to other races. Knowing Asian-American patients' ancestral country of origin may permit more precise estimation of their risks for OAG, NAG, and NTG.Financial disclosure(s)The authors have no proprietary or commercial interest in any materials discussed in this article.

Dataset Information

APOC3 genetic variation, serum triglycerides, and risk of coronary artery disease in Asian Indians, Europeans, and other ethnic groups.

Background

Methods

Results

Conclusions

Publications

APOC3 genetic variation, serum triglycerides, and risk of coronary artery disease in Asian Indians, Europeans, and other ethnic groups.

Similar Datasets

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