Soluble CD14 Levels in the Jackson Heart Study: Associations With Cardiovascular Disease Risk and Genetic Variants
| Autor: | Kendra Ferrier, Laura M. Raffield, Mindy D. Szeto, Paul L. Auer, Jonathan A. Shortt, Colton Leavitt, Leslie A. Lange, Nels C. Olson, Maggie A. Stanislawski, Alexander P. Reiner, Mariah Meyer, Russell P. Tracy, Timothy A. Thornton, Ethan M. Lange, Neil A. Zakai |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Time Factors CD14 Lipopolysaccharide Receptors Disease 030204 cardiovascular system & hematology Polymorphism Single Nucleotide Risk Assessment Article 03 medical and health sciences 0302 clinical medicine Mississippi Internal medicine medicine Humans Genetic Predisposition to Disease Stroke Subclinical infection Aged business.industry Incidence Hazard ratio Genetic variants Age Factors Middle Aged medicine.disease Prognosis Race Factors Black or African American 030104 developmental biology Cross-Sectional Studies Phenotype Cardiovascular Diseases Heart Disease Risk Factors Heart failure Disease risk Female Cardiology and Cardiovascular Medicine business Biomarkers Genome-Wide Association Study |
| Zdroj: | Arterioscler Thromb Vasc Biol |
| ISSN: | 1524-4636 |
| Popis: | Objective: sCD14 (soluble CD14) is a circulating pattern recognition receptor involved in inflammatory signaling. Although it is known that sCD14 levels vary by race, information on the genetic and cardiovascular disease (CVD) risk relationships of sCD14 in Black participants is limited. Approach and Results: We measured sCD14 in plasma at the baseline exam from n=3492 Black participants from the JHS (Jackson Heart Study). We evaluated associations between sCD14 and subclinical CVD measures, incident CVD events, and mortality under 3 levels of covariate adjustment. We used whole-genome sequence data from the Trans-Omics for Personalized Medicine program to identify genetic associations with sCD14. Adjusting for CVD risk factors and C-reactive protein, higher sCD14 was significantly associated with increased risk of mortality (hazard ratio, 1.25 [95% CI, 1.17–1.32]), incident coronary heart disease (hazard ratio, 1.28 [95% CI, 1.11–1.47]), and incident heart failure (hazard ratio, 1.27 [95% CI, 1.15–1.41]), but not stroke (hazard ratio, 0.96 [95% CI, 0.84–1.09]). Some of these relationships differed by age or sex: the association between sCD14 and heart failure was only observed in females; there was an association between sCD14 and stroke only at younger ages (in the lowest tertile of age, CD14 region of chromosome 5q31. We additionally identified 2 novel statistically distinct genetic associations with sCD14 represented by index variants rs770147646 and rs57599368, also in the chromosome 5q31 region. Conclusions: sCD14 independently predicts CVD-related outcomes and mortality in Black participants. |
| Databáze: | OpenAIRE |
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