The Association Between a Darc Gene Polymorphism and Clinical Outcomes in African American Patients With Acute Lung Injury

Kangelaris, Kirsten N.; Sapru, Anil; Calfee, Carolyn S.; Liu, Kathleen D.; Pawlikowska, Ludmila; Witte, John S.; Vittinghoff, Eric; Zhuo, Hanjing; Auerbach, Andrew D.; Ziv, Elad; Matthay, Michael A.

doi:10.1378/chest.11-1766

Cited by 58 publications

(43 citation statements)

References 54 publications

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“…53,54 Additionally, a polymorphism in the DARC gene resulting in a lack of the Duffy glycoprotein on RBCs is nearly exclusively found in individuals of African descent and has been associated with ARDS outcomes. 55 Genes involved in ABO antigen alterations or affecting overlapping mechanisms in the human body have the potential to alter the ancestryspecifi c association between ABO blood types and ARDS. Future studies in larger populations may assess these and other important genetic modifi ers.…”

Section: Discussionmentioning

confidence: 99%

ABO Blood Type A Is Associated With Increased Risk of ARDS in Whites Following Both Major Trauma and Severe Sepsis

Reilly

Meyer

Shashaty

et al. 2014

Chest

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Background: ABO glycosyltransferases catalyze antigen modifi cations on various glycans and glycoproteins and determine the ABO blood types. Blood type A has been associated with increased risk of vascular diseases and differential circulating levels of proteins related to infl ammation and endothelial function. The objective of this study was to determine the association of ABO blood types with ARDS risk in patients with major trauma and severe sepsis. Methods: We conducted prospective cohort studies in two populations at an urban tertiary referral, level I trauma center. Critically ill patients (n 5 732) presenting after major trauma were followed for 5 days for ARDS development. Additionally, 976 medical patients with severe sepsis were followed for 5 days for ARDS. Multivariable logistic regression was used to adjust for confounders. Results: ARDS developed in 197 of the 732 trauma patients (27%). Blood type A was associated with increased ARDS risk among whites (37% vs 24%; adjusted OR, 1.88; 95% CI, 1.14-3.12; P 5 .014), but not blacks (adjusted OR, 0.61; 95% CI, 0.33-1.13; P 5 .114). ARDS developed in 222 of the 976 patients with severe sepsis (23%). Blood type A was also associated with an increased ARDS risk among whites (31% vs 21%; adjusted OR, 1.67; 95% CI, 1.08-2.59; P 5 .021) but, again, not among blacks (adjusted OR, 1.17; 95% CI, 0.59-2.33; P 5 .652). Conclusions: Blood type A is associated with an increased risk of ARDS in white patients with major trauma and severe sepsis. These results suggest a role for ABO glycans and glycosyltransferases in ARDS susceptibility. CHEST 2014; 145(4):753-761Abbreviations: APACHE 5 Acute Physiology and Chronic Health Evaluation; ISS 5 injury severity score; MI 5 myocardial infarction; vWF 5 von Willebrand factor

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Section: Discussionmentioning

confidence: 99%

ABO Blood Type A Is Associated With Increased Risk of ARDS in Whites Following Both Major Trauma and Severe Sepsis

Reilly

Meyer

Shashaty

et al. 2014

Chest

View full text Add to dashboard Cite

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“…368 For example, a trio of coding single nucleotide polymorphisms in MYLK, the barrierregulatory gene encoding MLCK (discussed earlier), are rare in European descendants but frequent in those of African descent, and confer susceptibility to ARDS 369 and risk for severe asthma in African Americans. 370,371 Similarly, the functional rs2814778 polymorphism in the gene encoding the Duffy antigen/chemokine receptor is associated with worse clinical outcomes among African Americans with eFIGURE IMAGE GALLERY When interstitial water content increases, the matrix is disrupted and the exclusion volume decreases, making more of the matrix accessible to proteins. The increased distribution volume helps to maintain a lower concentration of protein and decreased colloid osmotic pressure than otherwise and constitutes an important edema safety factor opposing filtration.…”

Section: Pulmonary Vascular Genomics and Geneticsmentioning

confidence: 99%

Pulmonary Circulation and Regulation of Fluid Balance

Garcia¹

2016

Murray and Nadel's Textbook of Respiratory Medicine

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“…Individual susceptibility varies greatly, with patients presenting with the same severity score having markedly different clinical outcomes (6). For this reason, studies have begun to investigate the role of genetics in determining survival during ALI (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22).…”

mentioning

confidence: 99%

Functional Genomic Assessment of Phosgene-Induced Acute Lung Injury in Mice

Leikauf

Concel

Bein

et al. 2013

Am J Respir Cell Mol Biol

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In this study, a genetically diverse panel of 43 mouse strains was exposed to phosgene and genome-wide association mapping performed using a high-density single nucleotide polymorphism (SNP) assembly. Transcriptomic analysis was also used to improve the genetic resolution in the identification of genetic determinants of phosgene-induced acute lung injury (ALI). We prioritized the identified genes based on whether the encoded protein was previously associated with lung injury or contained a nonsynonymous SNP within a functional domain. Candidates were selected that contained a promoter SNP that could alter a putative transcription factor binding site and had variable expression by transcriptomic analyses. The latter two criteria also required that >10% of mice carried the minor allele and that this allele could account for >10% of the phenotypic difference noted between the strains at the phenotypic extremes. This integrative, functional approach revealed 14 candidate genes that included Atp1a1, Alox5, Galnt11, Hrh1, Mbd4, Phactr2, Plxnd1, Ptprt, Reln, and Zfand4, which had significant SNP associations, and Itga9, Man1a2, Mapk14, and Vwf, which had suggestive SNP associations. Of the genes with significant SNP associations, Atp1a1, Alox5, Plxnd1, Ptprt, and Zfand4 could be associated with ALI in several ways. Using a competitive electrophoretic mobility shift analysis, Atp1a1 promoter (rs215053185) oligonucleotide containing the minor G allele formed a major distinct faster-migrating complex. In addition, a gene with a suggestive SNP association, Itga9, is linked to transforming growth factor b1 signaling, which previously has been associated with the susceptibility to ALI in mice.

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The Association Between a Darc Gene Polymorphism and Clinical Outcomes in African American Patients With Acute Lung Injury

Cited by 58 publications

References 54 publications

ABO Blood Type A Is Associated With Increased Risk of ARDS in Whites Following Both Major Trauma and Severe Sepsis

ABO Blood Type A Is Associated With Increased Risk of ARDS in Whites Following Both Major Trauma and Severe Sepsis

Pulmonary Circulation and Regulation of Fluid Balance

Functional Genomic Assessment of Phosgene-Induced Acute Lung Injury in Mice

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