Division of Cardiology, Department of Internal Medicine, NewYork-Presbyterian Brooklyn Methodist Hospital, Brooklyn, NY 11215, USA.
Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Genes (Basel). 2024 Oct 27;15(11):1382. doi: 10.3390/genes15111382.
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. 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. Duffy null was strongly associated with higher hs-CRP (meta-analysis = 2.62 × 10), but the association was largely attenuated, though still marginally significant ( = 0.005), after conditioning on known 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. 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.
与其他美国人群相比，黑人群体的全因死亡率和心血管疾病（CVD）结局更差。在大多数黑人群体中，达菲趋化因子受体并不表达于红细胞上，但这一现象的临床意义尚不清楚。在这里，我们研究了达菲受体状态、高敏 C 反应蛋白（hs-CRP）与死亡率以及 CVD 事件（冠心病、中风和心力衰竭）的关系，研究对象为三个当代纵向队列研究（女性健康倡议、杰克逊心脏研究和动脉粥样硬化多民族研究）中自我认定的黑人群体成员。这项分析共纳入了 14358 名黑人群体参与者（9023 名达菲缺失，5335 名达菲受体阳性，这是根据单核苷酸多态性（SNP）rs2814778 定义的）。达菲缺失与更高的 hs-CRP 密切相关（荟萃分析 = 2.62×10），但在对与达菲基因连锁不平衡的已知基因座等位基因进行条件分析后，该关联虽仍有统计学意义（ = 0.005），但明显减弱。在我们的发现队列中，达菲缺失状态似乎与全因死亡率和中风发生率升高相关，但这些关联在调整包括 hs-CRP 在内的传统危险因素后减弱且无统计学意义。此外，在来自英国生物银行的黑人成年人的独立样本中，达菲缺失状态与死亡率的关联无法复制。这些发现表明，在达菲缺失个体中发现的更高水平的 hs-CRP，可能在一定程度上独立于已知影响 hs-CRP 循环水平的 CRP 等位基因。在对该基于社区的黑人群体参与者进行随访期间，达菲缺失状态与死亡率或 CVD 事件的发生无关，独立于包括 hs-CRP 在内的传统危险因素。
