Genetic architecture of cardiometabolic risks in people living with HIV

BMC Medicine

Jessica Williams-Nguyen¹  Bridget M. Whitney¹  Joseph A. Delaney¹  Inga Peter²  Won Jun Lee²  Haoxiang Chang²  Sierra R. White²  Ke Hao²  Robin M. Nance³  Anshuman Sewda⁴  Richard D. Moore⁵  Joseph J. Eron⁶  W. Christopher Mathews⁷  Paul K. Crane⁸  Mari M. Kitahata⁹  Heidi M. Crane⁹  Peter W. Hunt^1,10  Allison Webel^1,11  Amanda Willig^1,12  Michael S. Saag^1,12  Carla Marquez-Luna^1,13  Kenneth H. Mayer^1,14 

[1] Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, United States of America;Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, 10029, New York, NY, United States of America;Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, 10029, New York, NY, United States of America;Department of Medicine, University of Washington School of Medicine, Seattle, WA, United States of America;Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, 10029, New York, NY, United States of America;Institute of Health Management Research, IIHMR University, Jaipur, Rajasthan, India;Department of Medicine, Johns Hopkins University, Baltimore, MD, United States of America;Department of Epidemiology,

[2] Johns Hopkins University, Baltimore, MD, United States of America;Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, 27514, Chapel Hill, NC, United States of America;Department of Medicine, University of California San Diego, San Diego, CA, United States of America;Department of Medicine, University of Washington School of Medicine, Seattle, WA, United States of America;Department of Medicine, University of Washington School of Medicine, Seattle, WA, United States of America;Center for AIDS Research, University of Washington, Seattle, WA, United States of America;Division of Experimental Medicine, University of California San Francisco, San Francisco, CA, United States of America;Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, United States of America;School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States of America;The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America;The Fenway Institute at Fenway Health, Boston, MA, United States of America;

关键词: HIV;    Polygenic risk score;    Lipoprotein;    Triglyceride;    Type 2 diabetes;    Myocardial infarction;    Genome-wide association study;   

DOI  :  10.1186/s12916-020-01762-z

来源: Springer

【 摘 要 】

BackgroundAdvances in antiretroviral therapies have greatly improved the survival of people living with human immunodeficiency virus (HIV) infection (PLWH); yet, PLWH have a higher risk of cardiovascular disease than those without HIV. While numerous genetic loci have been linked to cardiometabolic risk in the general population, genetic predictors of the excessive risk in PLWH are largely unknown.MethodsWe screened for common and HIV-specific genetic variants associated with variation in lipid levels in 6284 PLWH (3095 European Americans [EA] and 3189 African Americans [AA]), from the Centers for AIDS Research Network of Integrated Clinical Systems cohort. Genetic hits found exclusively in the PLWH cohort were tested for association with other traits. We then assessed the predictive value of a series of polygenic risk scores (PRS) recapitulating the genetic burden for lipid levels, type 2 diabetes (T2D), and myocardial infarction (MI) in EA and AA PLWH.ResultsWe confirmed the impact of previously reported lipid-related susceptibility loci in PLWH. Furthermore, we identified PLWH-specific variants in genes involved in immune cell regulation and previously linked to HIV control, body composition, smoking, and alcohol consumption. Moreover, PLWH at the top of European-based PRS for T2D distribution demonstrated a > 2-fold increased risk of T2D compared to the remaining 95% in EA PLWH but to a much lesser degree in AA. Importantly, while PRS for MI was not predictive of MI risk in AA PLWH, multiethnic PRS significantly improved risk stratification for T2D and MI.ConclusionsOur findings suggest that genetic loci involved in the regulation of the immune system and predisposition to risky behaviors contribute to dyslipidemia in the presence of HIV infection. Moreover, we demonstrate the utility of the European-based and multiethnic PRS for stratification of PLWH at a high risk of cardiometabolic diseases who may benefit from preventive therapies.

【 授权许可】

CC BY