Racial and socioeconomic disparity associates with differences in cardiac DNA methylation among men with end-stage heart failure
| Autor: | Selwyn M. Vickers, Mark E Pepin, Salpy V. Pamboukian, Joseph Barchue, Chae-Myeong Ha, Ayman Haj Asaad, Sayan Bakshi, Steven M. Pogwizd, Bertha Hidalgo, Adam R. Wende, Luke A Potter |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Physiology Heart Ventricles 030204 cardiovascular system & hematology White People 03 medical and health sciences 0302 clinical medicine Physiology (medical) Internal medicine medicine Humans Epigenetics Promoter Regions Genetic Socioeconomic status Retrospective Studies Heart Failure DNA methylation Asian epigenetics business.industry Myocardium structural racism Racial Groups Editorial Focus Heart gene-environment interactions Middle Aged medicine.disease Black or African American 030104 developmental biology Socioeconomic Factors Heart failure Circulatory system Cardiology Racial differences End stage heart failure Cardiology and Cardiovascular Medicine business Research Article |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology Am J Physiol Heart Circ Physiol |
| ISSN: | 1522-1539 0363-6135 |
| Popis: | Heart failure (HF) is a multifactorial syndrome that remains a leading cause of worldwide morbidity. Despite its high prevalence, only half of patients with HF respond to guideline-directed medical management, prompting therapeutic efforts to confront the molecular underpinnings of its heterogeneity. In the current study, we examined epigenetics as a yet unexplored source of heterogeneity among patients with end-stage HF. Specifically, a multicohort-based study was designed to quantify cardiac genome-wide cytosine-p-guanine (CpG) methylation of cardiac biopsies from male patients undergoing left ventricular assist device (LVAD) implantation. In both pilot (n = 11) and testing (n = 31) cohorts, unsupervised multidimensional scaling of genome-wide myocardial DNA methylation exhibited a bimodal distribution of CpG methylation found largely to occur in the promoter regions of metabolic genes. Among the available patient attributes, only categorical self-identified patient race could delineate this methylation signature, with African American (AA) and Caucasian American (CA) samples clustering separately. Because race is a social construct, and thus a poor proxy of human physiology, extensive review of medical records was conducted, but ultimately failed to identify covariates of race at the time of LVAD surgery. By contrast, retrospective analysis exposed a higher all-cause mortality among AA (56.3%) relative to CA (16.7%) patients at 2 yr following LVAD placement (P = 0.03). Geocoding-based approximation of patient demographics uncovered disparities in income levels among AA relative to CA patients. Although additional studies are needed, the current analysis implicates cardiac DNA methylation as a previously unrecognized indicator of socioeconomic disparity in human heart failure outcomes. NEW & NOTEWORTHY A bimodal signature of cardiac DNA methylation in heart failure corresponds with racial differences in all-cause mortality following mechanical circulatory support. Racial differences in promoter methylation disproportionately affect metabolic signaling pathways. Socioeconomic factors are associated with racial differences in the cardiac methylome among men with end-stage heart failure. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/racial-socioeconomic-determinants-of-the-cardiac-epigenome/. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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