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A functional macrophage migration inhibitory factor promoter polymorphism is associated with reduced diffusing

C Zhang1, C Ramsey2, A Berical3

  • 1Department of Medicine Saint Louis University Hospital , Saint Louis, Missouri.

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A specific gene variant in macrophage migration inhibitory factor (MIF) is linked to reduced lung diffusion capacity in smokers. This finding may help explain why some individuals develop severe chronic obstructive pulmonary disease (COPD).

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COPDMIFdiffusion capacityemphysemamacrophage migration inhibitory factor

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Area of Science:

  • Pulmonary Medicine
  • Genetics
  • Immunology

Background:

  • Cigarette smoke is the primary modifiable risk factor for chronic obstructive pulmonary disease (COPD), but individual responses vary.
  • Macrophage migration inhibitory factor (MIF) is a cytokine involved in COPD pathogenesis.
  • A polymorphism in the MIF gene promoter (-794 CATT microsatellite repeat, rs5844572) influences MIF expression.

Purpose of the Study:

  • To investigate the association between the MIF-794 CATT microsatellite repeat polymorphism (rs5844572) and susceptibility to COPD-related traits.
  • To determine if this genetic variation impacts airflow obstruction and lung diffusion capacity.

Main Methods:

  • Cross-sectional analysis of DNA samples from 641 subjects.
  • Genotyping of the MIF-794 CATT5-8 microsatellite repeat polymorphism (rs5844572).
  • Multivariable logistic regression and generalized linear models to assess associations with airflow obstruction (FEV1/FVC <0.70) and diffusion capacity (DLCO % predicted <80%), and lung function parameters (FEV1 % predicted, DLCO % predicted).

Main Results:

  • The MIF-794 CATT5 allele was significantly associated with abnormal diffusion capacity in two independent cohorts (ORs ranging from 2.21 to 9.31).
  • Individuals with the MIF-794 CATT5 allele exhibited reduced DLCO % predicted compared to other genotypes (e.g., 63.5 vs. 70.0, P=0.0023).
  • No significant association was found with airflow obstruction.

Conclusions:

  • A common genetic polymorphism in the MIF gene (-794 CATT5 allele) is associated with reduced lung diffusion capacity (DLCO).
  • This genetic variation may contribute to COPD severity in smokers.
  • Further research is warranted to elucidate the mechanisms linking MIF genotype to impaired gas exchange.