Browsing by Author "Zhang, Weihua"

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    APOC3 genetic variation, serum triglycerides, and risk of coronary artery disease in Asian Indians, Europeans, and other ethnic groups
    (BioMed Central Ltd, 2021-09-21T00:00:00) 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.
    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).