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

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 316; no. 2; pp. L400 - L405
• Main Authors: Zhang, C, Ramsey, C, Berical, A, Yu, L, Leng, L, McGinnis, K A, Song, Y, Michael, H, McCormack, M C, Allore, H, Morris, A, Crothers, K, Bucala, R, Lee, P J, Sauler, M
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.02.2019
• Series: Translational Physiology
• Subjects: Air flow; Alleles; Carbon monoxide; Chronic obstructive pulmonary disease; Cigarette smoke; Confidence intervals; Deoxyribonucleic acid; Diffusion; DNA; Exposure; Forced Expiratory Volume - genetics; Gene expression; Gene polymorphism; Generalized linear models; Genetic Predisposition to Disease - genetics; Genotypes; Health risk assessment; Health risks; Leukocyte migration; Lung - metabolism; Lung diseases; Macrophage migration inhibitory factor; Macrophage Migration-Inhibitory Factors - genetics; Macrophage Migration-Inhibitory Factors - metabolism; Obstructive lung disease; Pathogenesis; Polymorphism; Polymorphism, Single Nucleotide - genetics; Promoter Regions, Genetic - genetics; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - metabolism; Rapid Report; Regression analysis; Regression models; Respiratory Function Tests; Risk analysis; Risk factors; Smoke; Smoke - adverse effects; Statistical analysis; Statistical models; Tobacco smoke; Vital Capacity - genetics; Vital Capacity - physiology; diffusion capacity; MIF; macrophage migration inhibitory factor; COPD; emphysema
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00439.2018

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 CATT microsatellite 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 CATT ( 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 (FEV )/forced vital capacity ratio <0.70] and an abnormal diffusion capacity [defined by a diffusion capacity for carbon monoxide (DL ) percent predicted <80%]. We then used generalized linear models to determine the association of MIF genotypes with FEV percent predicted and DL percent predicted. The MIF-794 CATT allele 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 CATT allele was associated with a reduced DL percentage 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 DL , an important measurement of COPD severity.