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Chest. 2012 May;141(5):1160-9. doi: 10.1378/chest.11-1766. Epub 2011 Dec 29.

The association between a Darc gene polymorphism and clinical outcomes in African American patients with acute lung injury.

Collaborators (189)

Hudson L, Hough C, Neff M, Sims K, Watkins T, Steingrub J, Tidswell M, DeSouza L, Kardos C, Kozikowski L, Kozikowski K, Guntupalli K, Bandi V, Pope C, Brower R, Fessler H, Hager D, Mendez-Tellez P, Oakjones K, Needham D, Sevransky J, Workneh A, Han S, Murray S, Shanholtz C, Netzer G, Rock P, Sampaio A, Titus J, Harrington T, Herr D, Lee B, Bolouri N, Wiedemann HP, Ashton RW, Culver DA, Frederick T, Komara JJ, Guzman JA, Reddy AJ, Hejal R, Andrews M, Haney D, Connors AF, Lasalvia S, Thornton J, Warren EL, Moss M, Benson A, Burnham E, Clark B, Gray L, Higgins C, Maloney BJ, Mealer M, Frankel S, Bost T, Dennen P, Hodgin K, Douglas I, Overdier K, Thompson K, Wolken R, MacIntyre N, Brown L, Cox C, Gentile M, Govert J, Knudsen N, Carson S, Chang L, Lanier J, Wheeler A, Bernard GR, Hays M, Mogan S, Rice T, Hite RD, Morris PE, Howard A, Harvey A, Bender K, Wright P, Gross S, McLean J, Overton A, Truwit J, Enfield K, Marshall M, Clemmer T, Weaver L, Zenger M, Krueger J, Morris A, Ahmed A, Austin A, Dean N, Grissom C, Hirshberg E, Kumar N, Miller R, Napoli L, Orme J, Pandita S, Schreiber G, Struck L, Thomas F, Thomsen G, Lawton C, Leung F, Kim P, Fujii T, Baughman J, Kerwin B, Hanselman D, Sundar K, Alward W, Hill T, Campbell E, Ludwig K, Nielsen D, Pearce M, Matthay MA, Calfee C, Daniel B, Eisner M, Garcia O, Johnson E, Kallet R, Kordesch K, Liu K, Zhou H, Peterson M, Blaauw J, Albertson T, Vlastelin E, Hubmayr R, Brown D, Gajic O, Hinds R, Holets S, Kor DJ, Passe M, deBoisblanc B, Lauto P, Romaine C, Meyaski G, Hunt J, Marr A, Long EK, Brierre S, LeBlanc C, Taylor D, Jain S, Seoane L, Simeone F, Fearon J, Duchesne J, Schoenfeld D, Aquino M, Dorer D, Guha M, Hammond E, Lavery N, Lazar P, Molina I, Morse R, Oldmixon C, Rawal B, Ringwood N, Shui A, Smoot E, Thompson BT, Harabin A, Bredow S, Waclawiw M, Weinmann G, Spragg RG, Slutsky A, Levy M, Markovitz B, Petkova E, Weijer C, Willson D, Sznajder J, Begg M, Israel E, Lewis J, Parsons P.

Author information

  • 1Department of Medicine, Division of General Internal Medicine, University of California, San Francisco, San Francisco, CA 94143-0131, USA. kkangelaris@medicine.ucsf.edu

Abstract

BACKGROUND:

Acute lung injury (ALI) mortality is increased among African Americans compared with Americans of European descent, and genetic factors may be involved. A functional T-46C polymorphism (rs2814778) in the promoter region of Duffy antigen/receptor for chemokines (Darc) gene, present almost exclusively in people of African descent, results in isolated erythrocyte DARC deficiency and has been implicated in ALI pathogenesis in preclinical and murine models, possibly because of an increase in circulating Duffy-binding, proinflammatory chemokines like IL-8. We sought to determine the effect of the functional rs2814778 polymorphism, C/C genotype (Duffy null state), on clinical outcomes in African Americans with acute lung injury.

METHODS:

Clinical data and biologic specimens from African American patients with ALI who enrolled in three randomized controlled trials were analyzed. Multivariate analysis accounted for proportion of African ancestry, sex, cirrhosis, and severity of illness on presentation.

RESULTS:

Among 132 subjects, 88 (67%) were Duffy null (C/C genotype). The Duffy null state was associated with a 17% absolute risk increase (95% CI, 1.4%-33%) in mortality at 60 days, a median of 8 fewer ventilator-free days (95% CI, 1-18.5), and 4.5 fewer organ failure-free days (95% CI, 0-18) compared with individuals with the C/T or T/T genotypes (all P values < .05). Estimates were similar on multivariate analysis. In African Americans without the null variant, clinical outcomes were similar to those in patients of European descent. A subgroup analysis suggested that plasma IL-8 levels are increased in Duffy null individuals.

CONCLUSIONS:

Our results provide evidence that the functional rs2814778 polymorphism in the gene encoding DARC is associated with worse clinical outcomes among African Americans with ALI, possibly via an increase in circulating IL-8.

Comment in

PMID:
22207676
[PubMed - indexed for MEDLINE]
PMCID:
PMC3342784
Free PMC Article

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