1. The Relationship of Duffy Gene Polymorphism with High-Sensitivity C-Reactive Protein, Mortality, and Cardiovascular Outcomes in Black Individuals
- Author
-
Ha, Edward T, Haessler, Jeffery, Taylor, Kent D, Tuftin, Bjoernar, Briggs, Matt, Parikh, Manish A, Peterson, Stephen J, Gerszten, Robert E, Wilson, James G, Kelsey, Karl, Tahir, Usman A, Seeman, Teresa, Rich, Stephen S, Carson, April P, Post, Wendy S, Kooperberg, Charles, Rotter, Jerome I, Raffield, Laura M, Auer, Paul, and Reiner, Alex P
- Subjects
Biological Sciences ,Genetics ,Prevention ,Atherosclerosis ,Heart Disease ,Cardiovascular ,Aging ,2.1 Biological and endogenous factors ,2.4 Surveillance and distribution ,Good Health and Well Being ,Humans ,Duffy Blood-Group System ,Female ,C-Reactive Protein ,Male ,Polymorphism ,Single Nucleotide ,Cardiovascular Diseases ,Aged ,Middle Aged ,Receptors ,Cell Surface ,Black or African American ,White ,Duffy receptor for chemokines ,atypical chemokine receptor 1 ,healthcare disparity ,hs-CRP ,Duffy gene polymorphism - Abstract
Background: Black adults have higher incidence of all-cause mortality and worse cardiovascular disease (CVD) outcomes when compared to other U.S. populations. The Duffy chemokine receptor is not expressed on erythrocytes in a large majority of Black adults, but the clinical implications of this are unclear. Methods: Here, we investigated the relationship of Duffy receptor status, high-sensitivity C-reactive protein (hs-CRP), and mortality and incident CVD events (coronary heart disease, stroke, and heart failure) in self-identified Black members of three contemporary, longitudinal cohort studies (the Women's Health Initiative, Jackson Heart Study, and Multi-Ethnic Study of Atherosclerosis). Data on 14,358 Black participants (9023 Duffy-null and 5335 Duffy-receptor-positive, as defined using single-nucleotide polymorphism (SNP) rs2814778) were included in this analysis. Results: Duffy null was strongly associated with higher hs-CRP (meta-analysis p = 2.62 × 10-9), but the association was largely attenuated, though still marginally significant (p = 0.005), after conditioning on known CRP locus alleles in linkage disequilibrium with the Duffy gene. In our discovery cohorts, Duffy-null status appeared to be associated with a higher risk of all-cause mortality and incident stroke, though these associations were attenuated and non-significant following adjustment for traditional risk factors including hs-CRP. Moreover, the association of Duffy-null status with mortality could not be replicated in an independent sample of Black adults from the UK Biobank. Conclusions: These findings suggest that the higher levels of hs-CRP found in Duffy-null individuals may be in part independent of CRP alleles known to influence circulating levels of hs-CRP. During the follow-up of this community-based sample of Black participants, Duffy-null status was not associated with mortality or incident CVD events independently of traditional risk factors including hs-CRP.
- Published
- 2024