Browsing by Author "Almeida, Marcio"

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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).
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    Burden of Type 2 Diabetes and Associated Cardiometabolic Traits and Their Heritability Estimates in Endogamous Ethnic Groups of India: Findings From the INDIGENIUS Consortium
    (Frontiers Media S.A., 2022-04-14T00:00:00) Venkatesan, Vettriselvi; Lopez-Alvarenga, Juan Carlos; Arya, Rector; Ramu, Deepika; Koshy, Teena; Ravichandran, Umarani; Ponnala, Amaresh Reddy; Sharma, Surendra K.; Lodha, Sailesh; Sharma, Krishna K.; Shaik, Mahaboob Vali; Resendez, Roy G.; Venugopal, Priyanka; Parthasarathy, R.; Saju, Noelta; Ezeilo, Juliet A.; Bejar, Cynthia; Wander, Gurpreet S.; Ralhan, Sarju; Singh, Jai Rup; Mehra, Narinder K.; Vadlamudi, Raghavendra Rao; Almeida, Marcio; Mummidi, Srinivas; Natesan, Chidambaram; Blangero, John; Medicherla, Krishna M.; Thanikachalam, Sadagopan; Panchatcharam, Thyagarajan Sadras; Kandregula, Dileep Kumar; Gupta, Rajeev; Sanghera, Dharambir K.; Duggirala, Ravindranath; Paul, Solomon F. D.
    To assess the burden of type 2 diabetes (T2D) and its genetic profile in endogamous populations of India given the paucity of data, we aimed to determine the prevalence of T2D and estimate its heritability using family-based cohorts from three distinct Endogamous Ethnic Groups (EEGs) representing Northern (Rajasthan [Agarwals: AG]) and Southern (Tamil Nadu [Chettiars: CH] and Andhra Pradesh [Reddys: RE]) states of India. For comparison, family-based data collected previously from another North Indian Punjabi Sikh (SI) EEG was used. In addition, we examined various T2D-related cardiometabolic traits and determined their heritabilities. These studies were conducted as part of the Indian Diabetes Genetic Studies in collaboration with US (INDIGENIUS) Consortium. The pedigree, demographic, phenotypic, covariate data and samples were collected from the CH, AG, and RE EEGs. The status of T2D was defined by ADA guidelines (fasting glucose ? 126 mg/dl or HbA1c ? 6.5% and/or use of diabetes medication/history). The prevalence of T2D in CH (N = 517, families = 21, mean age = 47y, mean BMI = 27), AG (N = 530, Families = 25, mean age = 43y, mean BMI = 27), and RE (N = 500, Families = 22, mean age = 46y, mean BMI = 27) was found to be 33%, 37%, and 36%, respectively, Also, the study participants from these EEGs were found to be at increased cardiometabolic risk (e.g., obesity and prediabetes). Similar characteristics for the SI EEG (N = 1,260, Families = 324, Age = 51y, BMI = 27, T2D = 75%) were obtained previously. We used the variance components approach to carry out genetic analyses after adjusting for covariate effects. The heritability (h2) estimates of T2D in the CH, RE, SI, and AG were found to be 30%, 46%, 54%, and 82% respectively, and statistically significant (P ? 0.05). Other T2D related traits (e.g., BMI, lipids, blood pressure) in AG, CH, and RE EEGs exhibited strong additive genetic influences (h2 range: 17% [triglycerides/AG and hs-CRP/RE] - 86% [glucose/non-T2D/AG]). Our findings highlight the high burden of T2D in Indian EEGs with significant and differential additive genetic influences on T2D and related traits. Copyright � 2022 Venkatesan, Lopez-Alvarenga, Arya, Ramu, Koshy, Ravichandran, Ponnala, Sharma, Lodha, Sharma, Shaik, Resendez, Venugopal, R, Saju, Ezeilo, Bejar, Wander, Ralhan, Singh, Mehra, Vadlamudi, Almeida, Mummidi, Natesan, Blangero, Medicherla, Thanikachalam, Panchatcharam, Kandregula, Gupta, Sanghera, Duggirala and Paul.