RT Journal Article
SR Electronic
T1 Macrophage migration inhibitory factor (<em>MIF</em>) promoter polymorphisms are associated with favorable hemodynamic indices in systemic sclerosis-associated pulmonary arterial hypertension
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P3171
VO 40
IS Suppl 56
A1 Todd Kolb
A1 Danielle Boyce
A1 Noah Lechtzin
A1 Nicholas Rafaels
A1 Li Gao
A1 Kathleen Barnes
A1 Reda Girgis
A1 Ari Zaiman
A1 Stephen Mathai
A1 Laura Hummers
A1 Traci Housten
A1 Rachel Damico
A1 Paul Hassoun
YR 2012
UL http://erj.ersjournals.com/content/40/Suppl_56/P3171.abstract
AB RATIONALE: Inflammatory mediators are increasingly associated with pathogenesis in pulmonary arterial hypertension (PAH). We have previously observed a 3.7-fold increase in serum levels of the pro-inflammatory macrophage migration inhibitory factor (MIF) in PAH patients. MIF promoter polymorphisms (-173*C, -794CATT5-8) have been associated with disease susceptibility or phenotype in several inflammatory syndromes. We hypothesized that MIF promoter polymorphisms may influence PAH development or severity.METHODS: Genomic DNA was isolated from 117 European-American PAH patients, including idiopathic (IPAH; N = 35) and systemic sclerosis-associated PAH (SSc-PAH; N = 82), healthy European-American controls (N=264), and SSc patients without PAH (N=343). Allele and genotype frequencies for the MIF -173*C single nucleotide polymorphism and the -794CATT5-8 variable nucleotide tandem repeat were compared between PAH patients and controls, and were compared with initial hemodynamic indices and survival in PAH patients.RESULTS: We found no significant difference in the frequencies of either MIF promoter polymorphism between controls and PAH patients. SSc-PAH patients with the MIF -173*C polymorphism had higher cardiac output (P=0.04), cardiac index (P=0.003), and stroke volume index (P=0.01) at diagnosis. Neither polymorphism predicted survival in PAH patients.CONCLUSION: The MIF -173*C polymorphism may improve initial hemodynamics in SSc-PAH. However, MIF promoter polymorphisms do not predict PAH susceptibility or survival. These results suggest that MIF may function as a disease-modifying gene in SSc-PAH.