The Relationship of Duffy Gene Polymorphism, High Sensitivity C-Reactive Protein, and Long-term Outcomes
Author:
Ha Edward T., Taylor Kent D.ORCID, Raffield Laura M, Briggs Matt, Yee Aaron, Elemento Olivier, Parikh Manish, Peterson Stephen J., Frishman William, Gerszten Robert E.ORCID, Wilson James G., Kelsey KarlORCID, Tahir Usman A., Reiner AlexORCID, Auer Paul, Seeman Teresa, Rich Stephen S.ORCID, Carson April P.ORCID, Post Wendy S.ORCID, Rotter Jerome I.ORCID, Aronow Wilbert S.
Abstract
AbstractBackgroundBlack adults have higher incidence of all-cause death and worse cardiovascular outcomes when compared to other populations. The Duffy chemokine receptor is not expressed in a large majority of Black adults and the clinical implications of this are unclear.MethodsHere, we investigated the relationship of Duffy receptor status, high-sensitivity C-reactive protein (hs-CRP), and long-term cardiovascular outcomes in Black members of two contemporary, longitudinal cohort studies (the Jackson Heart Study and Multi-Ethnic Study of Atherosclerosis). Data on 4,307 Black participants (2,942 Duffy null and 1,365 Duffy receptor positive, as defined using Single Nucleotide Polymorphism (SNP) rs2814778) were included in this analysis.ResultsDuffy null was not independently associated with elevated levels of serum hs-CRP levels once conditioning for knownCRPlocus alleles in linkage disequilibrium with the Duffy gene. Duffy null status was not found to be independently associated with higher incidence of all-cause mortality or secondary outcomes after adjusting for possible confounders in Black participants.ConclusionsThese findings suggest that increased levels of hs-CRP found in Duffy null individuals is due to co-inheritance of CRP alleles known to influence circulating levels hs-CRP and that Duffy null status was not associated with worse adverse outcomes over the follow-up period in this cohort of well-balanced Black participants.
Publisher
Cold Spring Harbor Laboratory
Reference20 articles.
1. Fujishiro K , Hajat A , Landsbergis PA , Meyer JD , Schreiner PJ , Kaufman JD . Explaining racial/ethnic differences in all-cause mortality in the Multi-Ethnic Study of Atherosclerosis (MESA): Substantive complexity and hazardous working conditions as mediating factors. SSM Popul Health 2017;3. 2. Popejoy AB , Fullerton SM . Genomics is failing on diversity. Nature 2016;538. 3. Reich D , Nalls MA , Kao WHL , Akylbekova EL , Tandon A , Patterson N , Mullikin J , Hsueh WC , Cheng CY , Coresh J , Boerwinkle E , Li M , Waliszewska A , Neubauer J , Li R , Leak TS , Ekunwe L , Files JC , Hardy CL , Zmuda JM , Taylor HA , Ziv E , Harris TB , Wilson JG . Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene. PLoS Genet 2009;5. 4. Kim S , Eliot M , Koestler DC , Wu WC , Kelsey KT . Association of neutrophil-to-lymphocyte ratio with mortality and cardiovascular disease in the jackson heart study and modification by the duffy antigen variant. JAMA Cardiol 2018;3. 5. Wang J , Ou ZL , Hou YF , Luo JM , Shen ZZ , Ding J , Shao ZM . Enhanced expression of Duffy antigen receptor for chemokines by breast cancer cells attenuates growth and metastasis potential. Oncogene 2006;25.
|
|