Polygenic risk scores point toward potential genetic mechanisms of type 2 myocardial infarction in people with HIV

Lee, Won Jun and Cheng, Haoxiang and Whitney, Bridget M. and Nance, Robin M. and Britton, Sierra R. and Jordahl, Kristina and Lindstrom, Sara and Ruderman, Stephanie A. and Kitahata, Mari M. and Saag, Michael S. and Willig, Amanda L. and Burkholder, Greer and Eron, Joseph J. and Kovacic, Jason C. and Björkegren, Johan L.M. and Mathews, W. Christopher and Cachay, Edward and Feinstein, Matthew J. and Budoff, Mathew and Hunt, Peter W. and Moore, Richard D. and Keruly, Jeanne and McCaul, Mary E. and Chander, Geetanjali and Webel, Allison and Mayer, Kenneth H. and Delaney, Joseph A. and Crane, Paul K. and Martinez, Claudia and Crane, Heidi M. and Hao, Ke and Peter, Inga (2023) Polygenic risk scores point toward potential genetic mechanisms of type 2 myocardial infarction in people with HIV. International Journal of Cardiology, 383. pp.15-23. ISSN 01675273

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Link to published document: http://doi.org/10.1016/j.ijcard.2023.04.058

Abstract

BACKGROUND: People with human immunodeficiency virus (HIV) infection (PWH) are at higher risk of myocardial infarction (MI) than those without HIV. About half of MIs in PWH are type 2 (T2MI), resulting from mismatch between myocardial oxygen supply and demand, in contrast to type 1 MI (T1MI), which is due to primary plaque rupture or coronary thrombosis. Despite worse survival and rising incidence in the general population, evidence-based treatment recommendations for T2MI are lacking. We used polygenic risk scores (PRS) to explore genetic mechanisms of T2MI compared to T1MI in PWH. METHODS: We derived 115 PRS for MI-related traits in 9541 PWH enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems cohort with adjudicated T1MI and T2MI. We applied multivariate logistic regression analyses to determine the association with T1MI and T2MI. Based on initial findings, we performed gene set enrichment analysis of the top variants composing PRS associated with T2MI. RESULTS: We found that T1MI was strongly associated with PRS for cardiovascular disease, lipid profiles, and metabolic traits. In contrast, PRS for alcohol dependence and cholecystitis, significantly enriched in energy metabolism pathways, were predictive of T2MI risk. The association remained after the adjustment for actual alcohol consumption. CONCLUSIONS: We demonstrate distinct genetic traits associated with T1MI and T2MI among PWH further highlighting their etiological differences and supporting the role of energy regulation in T2MI pathogenesis.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 10 Jul 2023 03:53
Last Modified: 10 Jul 2023 04:59
URI: http://eprints.victorchang.edu.au/id/eprint/1412

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