A functional macrophage migration inhibitory factor promoter polymorphism is associated with reduced diffusing capacity
Abstract
Cigarette smoke exposure is the leading modifiable risk factor for chronic obstructive pulmonary disease (COPD); however, the clinical and pathologic consequences of chronic cigarette smoke exposure are variable among smokers. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine implicated in the pathogenesis of COPD. Within the promoter of the MIF gene is a functional polymorphism that regulates MIF expression (-794 CATT5–8microsatellite repeat) ( rs5844572 ). The role of this polymorphim in mediating disease susceptibility to COPD-related traits remains unknown. We performed a cross-sectional analysis of DNA samples from 641 subjects to analyze MIF-794 CATT5–8( rs5844572 ) polymorphism by standard methods. We generated multivariable logistic regression models to determine the risk of low expressing MIF alleles for airflow obstruction [defined by forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio CO) percent predicted 1percent predicted and DLCOpercent predicted. The MIF-794 CATT5allele was associated with an abnormal diffusion capacity in two cohorts [odds ratio (OR): 9.31, 95% confidence interval (CI): 1.97–4.06; and OR: 2.21, 95% CI: 1.03–4.75]. Similarly, the MIF-794 CATT5allele was associated with a reduced DLCOpercentage predicted in these two cohorts: 63.5 vs. 70.0 ( P = 0.0023) and 60.1 vs. 65.4 ( P = 0.059). This study suggests an association between a common genetic polymorphism of an endogenous innate immune gene, MIF, with reduced DLCO, an important measurement of COPD severity.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 01, 2019
- Source ID
- 10.1152/ajplung.00439.2018
Entities
People
- A. Berical
- A. Morris
- C. Ramsey
- C. Zhang
- H. Allore
- H. Michael
- K. A. Mcginnis
- K. Crothers
- L. Leng
- L. Yu
- M. C. Mccormack
- Maor Sauler
- Peter J. Lee
- R. Bucala
- Yiwen Song
Organizations
- Boston University
- FAMRI
- Johns Hopkins University
- Massachusetts General Hospital
- National Institutes of Health
- Saint Louis University Hospital
- United States Department of Defense
- University of Pittsburgh
- University of Washington
- Yale School of Medicine