Macrophage Migration Inhibitory Factor Polymorphism Is Associated with Susceptibility to Inflammatory Coronary Heart Disease

Abstract

Background. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine. This study explored the association of 173G/C polymorphism of the MIF gene with coronary heart disease (CHD). Methods. Sequencing was carried out after polymerase chain reaction with DNA specimens from 186 volunteers without CHD and 70 patients with CHD. Plasma MIF levels on admission were measured by ELISA. Patients were classified into either stable angina pectoris (SAP) or unstable angina pectoris (UAP). Genotype distribution between cases and controls and the association of patients' genotypes with MIF level and plaque stability were statistically evaluated (ethical approval number: 2012-01). Results. The frequency of the C genotype was higher in CHD patients than in the control (P = 0.014). The frequency of the 173*CC genotype was higher in CHD patients than in the control (P = 0.005). The plasma MIF level was higher in MIF173*C carriers than in MIF173*G carriers (P = 0.033). CHD patients had higher plasma MIF levels than the control (P = 0.000). Patients with UAP had higher plasma MIF levels than patients with SAP (P = 0.014). Conclusions. These data suggest that MIF −173G/C polymorphism may be related to the development of CHD in a Chinese population. Plasma MIF level is a predictor of plaque stability. This trial is registered with NCT01750502 .

Macrophage migration inhibitory factor promoter polymorphisms (−794 CATT5–8): Relationship with soluble MIF levels in coronary atherosclerotic disease subjects

“…Previous studies have reported that the plasma MIF level of CAD group was higher than non-CAD patients and the plasma MIF level was related to the stability of the plaque [12]. Also, we demonstrated a close association between the polymorphism of MIF on the −173 position and CAD [12].…”

MIF family cytokines in cardiovascular diseases and prospects for precision-based therapeutics

“…These findings were recently affirmed in two studies of Chinese populations [54, 55]. In a Mexican-Mestizo population, the frequency of the −794 CATT 6/7 genotype also was significantly higher in patients with acute coronary artery syndromes when compared to healthy subjects (OR=1.77) [56].…”

Association of macrophage migration inhibitory factor promoter polymorphism –173G/C with susceptibility to childhood asthma

“…Healthy individuals carrying the MIF-173C allele produce greater amounts of MIF protein compared with those with the MIF-GG genotype, and their serum MIF levels are significantly higher [8]. Furthermore, studies have shown that patients with severe asthma have higher serum MIF levels than those with mild asthma [17, 18].…”

“…The MIF gene maps to chromosome 22q11.2 in humans. Functional polymorphisms have been identified in the MIF promoter region: a single nucleotide polymorphism (SNP) at position –173 [guanine (G)-to-cytosine (C) transition] and a CATT 5–8 microsatellite polymorphism at position –794 [8]. Polymorphisms of the human MIF gene have been associated with increased susceptibility to or severity of a number of inflammatory and autoimmune diseases such as juvenile idiopathic and adult rheumatoid arthritis, ulcerative colitis, atopy, sarcoidosis, psoriasis and extensive forms of alopecia areata [8–10].…”

“…Treatment with anti-MIF antibody significantly suppressed airway inflammation and airway hyperresponsiveness in rats with atopic asthma [12]. Polymorphism in the –173C allele has been associated with higher transcription activity of the MIF gene and increased production of MIF protein, while the CATT 5 allele has the lowest level of basal and stimulated MIF promoter activity in vitro compared with other alleles [8]. So far, the associations between MIF-173G/C promoter polymorphism and asthma have not been fully studied.…”