A Common Blood Group Type (Duffy Null) in African Americans Predicts Increased Mortality in Acute Lung Injury

1University of California, San Francisco, San Francisco, CA
2University of California, San Francisco, San Francisco, CA
3University of California, San Francisco, San Francisco, CA
4University of California, San Francisco, San Francisco, CA
5University of California, San Francisco, San Francisco, CA
6University of California, San Francisco, San Francisco, CA
7University of California, San Francisco, San Francisco, CA
8University of California, San Francisco, San Francisco, CA
9University of California, San Francisco, San Francisco, CA
10University of California, San Francisco, San Francisco, CA

Meeting: Hospital Medicine 2010, April 8-11, Washington, D.C.

Abstract number: 74

Background:

African Americans suffer nearly double the annual estimated mortality rate of whites in acute lung injury (ALI), and genetic factors may be involved The Duffy blood group antigen is a chemokine receptor on red blood cells, and although present almost universally in whites, it is absent in two thirds of African Americans. This so‐called Duffy‐null state is caused by a single gene variant, and mouse models suggest it may be involved in the pathogenesis of ALI. We sought to determine whether the Duffy‐null state was associated with clinical outcomes among African Americans with ALI.

Methods:

We genotyped 132 African American patients from 3 Acute Respiratory Distress Syndrome Network trials for the Darc ‐46 C/T gene single nucleotide polymorphism (rs2814778). By convention, patients with 2 copies of this polymorphism were labeled “Duffy null,” whereas patients with 1 or 0 copies were labeled “Duffy positive,” Outcomes included (1) ventilator‐free days (VFDs) to day 28, a composite end point including days free of mechanical ventilation (0‐28) in survivors or death within 28 days (VFD = 0), where a lower number signifies worse outcomes; and (2) mortality at 60 days. We adjusted for African ancestry using ancestry informative markers across the genome. We compared number of VFDs and 60‐day mortality by Darc genotype using the Wilcoxon rank sum test and the chi‐square test, respectively. We then used logistic regression and ordinal regression models to test for associations between the Duffy‐null state and clinical outcomes after adjusting for ancestry.

Results:

Of 132 participants, 88 (67%) were Duffy null. In unadjusted analysis, Duffy null patients had fewer ventilator‐free days (median of 13 vs. 21 days, P = 0.04), and higher mortality rates (38% versus 20%, P = 0.04) than their Duffy‐positive counterparts. Duffy‐null individuals were found to have a twofold increased odds of being in a lower ventilator‐free day quintile (OR 2.0, 95% Cl 1.0–3.9) and a 2.3‐fold increased odds of mortality compared with Duffy‐positive individuals (OR 2.3, 95% Cl 1.0–5.5) These estimates did not change in our adjusted model (Table 1).

Conclusions:

The Duffy‐null state is associated with increased mechanical ventilation requirements and increased mortality in African American patients with acute lung injury. The association persists after adjusting for African ancestry. Our findings suggest that the Duffy‐null state plays a role in the pathogenesis of acute lung injury and may account for some of the increased mortality observed among African American patients. Future work will determine if lesting for the Duffy blood group antigen in African Americans presenting with ALI may provide additive prognostic information over clinical algorithms alone.

Author Disclosure:

K. Kangelaris, none; A. Sapru, none; C. Calfee, none; K. Liu, none; A. Auerbach, none; J. Witte, none; E. Vittinghoff, none; H. Zhuo, none; E. Ziv, none; M. Matthay, none.

To cite this abstract:

Kangelaris K, Sapru A, Calfee C, Liu K, Auerbach A, Witte J, Vlttinghoff E, Zhuo H, Ziv E, Matthay M. A Common Blood Group Type (Duffy Null) in African Americans Predicts Increased Mortality in Acute Lung Injury. Abstract published at Hospital Medicine 2010, April 8-11, Washington, D.C. Abstract 74. Journal of Hospital Medicine. 2010; 5 (suppl 1). https://www.shmabstracts.com/abstract/a-common-blood-group-type-duffy-null-in-african-americans-predicts-increased-mortality-in-acute-lung-injury/. Accessed June 19, 2019.

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