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APOC3 genetic variation, serum triglycerides, and risk of coronary artery disease in Asian Indians, Europeans, and other ethnic groups.
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- معلومة اضافية
- المصدر:
Publisher: BioMed Central Country of Publication: England NLM ID: 101147696 Publication Model: Electronic Cited Medium: Internet ISSN: 1476-511X (Electronic) Linking ISSN: 1476511X NLM ISO Abbreviation: Lipids Health Dis Subsets: MEDLINE
- بيانات النشر:
Original Publication: [London] : BioMed Central, 2002-
- الموضوع:
- نبذة مختصرة :
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).)
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- Grant Information:
212945/Z/18/Z United Kingdom WT_ Wellcome Trust; G0700931 United Kingdom MRC_ Medical Research Council; G0601966 United Kingdom MRC_ Medical Research Council; R01DK118427 United States DK NIDDK NIH HHS; NOT-HG-11-009 United States HG NHGRI NIH HHS; R01DK082766 United States NH NIH HHS
- Contributed Indexing:
Keywords: ApoC-III; Asian Indians; Coronary artery disease risk; Mendelian randomization; Rare and common variants; Triglyceride
- الرقم المعرف:
0 (APOC3 protein, human)
0 (Apolipoprotein C-III)
0 (Triglycerides)
- الموضوع:
Date Created: 20210922 Date Completed: 20220221 Latest Revision: 20240214
- الموضوع:
20240214
- الرقم المعرف:
PMC8456544
- الرقم المعرف:
10.1186/s12944-021-01531-8
- الرقم المعرف:
34548093
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