The influence of macrophage migration inhibitory factor gene polymorphisms on outcome from community-acquired pneumonia

Sachin Yende, Derek C. Angus, Lan Kong, John A. Kellum, Lisa Weissfeld, Robert Ferrell, David Finegold, Melinda Carter, Lin Leng, Zhi Yong Peng, Richard Bucala

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

The cytokine, macrophage migration inhibitory factor (MIF), is encoded in a functionally polymorphic locus and subjects with high-expression MIF alleles are at an increased risk of inflammatory disease. Severe sepsis is the leading cause of death in intensive care units, and the prevailing hypothesis is that an excessive innate response contributes to its pathogenesis. To assess if MIF alleles influence the clinical course of infection, we conducted a case-control study to assess susceptibility and a parallel inception cohort study of community-acquired pneumonia (CAP) to assess risk of severe sepsis and 90-d mortality. Two distinct polymorphisms in the MIF promoter were analyzed: a G/C transition at -173 and a CATT repeat at -794. The frequency of both polymorphisms was similar in the CAP cohort (n=1739) and controls (n=639); however, the 90-d mortality was lower for the high-expression C allele (P=0.003). This association remained significant after adjusting for demographics, comorbid conditions, and disease severity score [hazard ratio=0.64 (0.44-0.91), P=0.01]. The hazard ratio was similar in different geographic subcohorts, and the association remained significant after adjusting for false discovery. These data indicate that polymorphisms associated with higher MIF expression may have a beneficial effect in community-acquired pneumonia.

Original languageEnglish (US)
Pages (from-to)2403-2411
Number of pages9
JournalFASEB Journal
Volume23
Issue number8
DOIs
StatePublished - Aug 1 2009

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Macrophage Migration-Inhibitory Factors
Polymorphism
Pneumonia
Genes
Alleles
Sepsis
Hazards
Intensive care units
Mortality
Intensive Care Units
Case-Control Studies
Cause of Death
Cohort Studies
Demography
Cytokines
Infection

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Yende, Sachin ; Angus, Derek C. ; Kong, Lan ; Kellum, John A. ; Weissfeld, Lisa ; Ferrell, Robert ; Finegold, David ; Carter, Melinda ; Leng, Lin ; Peng, Zhi Yong ; Bucala, Richard. / The influence of macrophage migration inhibitory factor gene polymorphisms on outcome from community-acquired pneumonia. In: FASEB Journal. 2009 ; Vol. 23, No. 8. pp. 2403-2411.
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Yende, S, Angus, DC, Kong, L, Kellum, JA, Weissfeld, L, Ferrell, R, Finegold, D, Carter, M, Leng, L, Peng, ZY & Bucala, R 2009, 'The influence of macrophage migration inhibitory factor gene polymorphisms on outcome from community-acquired pneumonia', FASEB Journal, vol. 23, no. 8, pp. 2403-2411. https://doi.org/10.1096/fj.09-129445

The influence of macrophage migration inhibitory factor gene polymorphisms on outcome from community-acquired pneumonia. / Yende, Sachin; Angus, Derek C.; Kong, Lan; Kellum, John A.; Weissfeld, Lisa; Ferrell, Robert; Finegold, David; Carter, Melinda; Leng, Lin; Peng, Zhi Yong; Bucala, Richard.

In: FASEB Journal, Vol. 23, No. 8, 01.08.2009, p. 2403-2411.

Research output: Contribution to journalArticle

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T1 - The influence of macrophage migration inhibitory factor gene polymorphisms on outcome from community-acquired pneumonia

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AU - Angus, Derek C.

AU - Kong, Lan

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AU - Weissfeld, Lisa

AU - Ferrell, Robert

AU - Finegold, David

AU - Carter, Melinda

AU - Leng, Lin

AU - Peng, Zhi Yong

AU - Bucala, Richard

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AB - The cytokine, macrophage migration inhibitory factor (MIF), is encoded in a functionally polymorphic locus and subjects with high-expression MIF alleles are at an increased risk of inflammatory disease. Severe sepsis is the leading cause of death in intensive care units, and the prevailing hypothesis is that an excessive innate response contributes to its pathogenesis. To assess if MIF alleles influence the clinical course of infection, we conducted a case-control study to assess susceptibility and a parallel inception cohort study of community-acquired pneumonia (CAP) to assess risk of severe sepsis and 90-d mortality. Two distinct polymorphisms in the MIF promoter were analyzed: a G/C transition at -173 and a CATT repeat at -794. The frequency of both polymorphisms was similar in the CAP cohort (n=1739) and controls (n=639); however, the 90-d mortality was lower for the high-expression C allele (P=0.003). This association remained significant after adjusting for demographics, comorbid conditions, and disease severity score [hazard ratio=0.64 (0.44-0.91), P=0.01]. The hazard ratio was similar in different geographic subcohorts, and the association remained significant after adjusting for false discovery. These data indicate that polymorphisms associated with higher MIF expression may have a beneficial effect in community-acquired pneumonia.

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