Macrophage Migration Inhibitory Factor Gene Polymorphisms Research Articles

Macrophage Migration Inhibitory Factor Gene Polymorphism in Acute Coronary Syndrome.

Background Acute coronary syndrome (ACS) is a result of the interplay between genetic and environmental risk factors. A unique cytokine macrophage migration inhibitory factor (MIF), expressed by inflammatory cells, acts via a cluster of differentiation 74 (CD74) and a cluster of differentiation 44 (CD44) receptors, leading to the recruitment of mononuclear neutrophils and lymphocytes. This cascade results in exaggerated inflammation and atherosclerosis. MIF's distinctive characteristics and functions make it an essential target for achieving therapeutic atherosclerosis regression, setting it apart from other cytokines. Hence, this study aims to detect the MIF gene polymorphism in ACS patientsand to assess the incidence of in-hospital major adverse cardiac events (MACE). Methodology This study was conducted in a tertiary care hospital. A total of 90 patients who had ACS were enrolled, of which 83 were included, and seven patients were excluded based on exclusion criteria (four cases of old myocardial infarction, two cases of valvular heart disease, and one case of dilated cardiomyopathy). After detailed clinical examination, laboratory evaluation, and genetic test, patients were divided into two groups based on MIF gene mutation. Five patients who had positive MIF gene mutationwere termed as group A (n=5), and 78 patients with negative MIF gene mutation were termed as group B (n=78). The statistical analysis for the collected data was done using IBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, New York, USA). Results Out of the 83 patients in this study, the male gender was predominant; there were three male patients in group A (n=3; 60%) and 48 male patients in group B (n=48; 61.5%). The most common age group was between 60 and 69 years; two of five patients (n=2; 40%) in group A and 30 out of 78 patients (n=30; 38.4%) in group B belonged to this age group. The common symptomwas chest pain present infive patients in group A (n=5; 100%) and 76 patients (n=76; 97.5%) in group B. A common risk factor in group A patientswas tobacco chewing, seen in three patients (n=3; 60%), and group B smoking was the most common risk factor seen in 30 patients (n=30; 38.5%). The most common ECG finding in group A was ST-elevation myocardial infarction (STEMI), seen in three patients(n=3; 60%), and in group B, the commonest ECG finding was non-ST-elevation myocardial infarction (NSTEMI) seen in 23 patients (n=23; 29.5%). The most common MACE was heart failure seen in two patients in group A (n=2; 40%) and in 50 patients in group B (n=50; 64.1%), followed by arrhythmias seen in one patient in group A (n=1; 20%), and eight patients in group B (n=8; 10.3%). Conclusion This study demonstrated a significant positive association betweenMIF gene polymorphism and the occurrence of cardiovascular events like myocardial infarction, with a statistically significant p-value (p=0.001). This study showed the presence of the disease in young age groups and individuals without conventional risk factors, underscoring the importance of genetic studies. Genetic risk factors independently contribute to the pathophysiology of coronary artery disease; hence, understanding the mechanisms of these genes and incorporating genetic testing into standard clinical practice can help future research to developtherapeutic agents that can specifically target these genes.

Haplotypes of [-794(CATT)5-8 /-173G>C] MIF gene polymorphisms and its soluble levels in cutaneous squamous cell carcinoma in western Mexican population.

Some cytokines are strongly implicated in the development of squamous cell carcinoma (SCC) such as the Macrophage migration inhibitory factor (MIF). The haplotype -794 (CATT)5-8 /-173G>C in MIF gene polymorphisms has been associated with some types of cancer. The aim of this study is to establish the possible association between the presence of this haplotype in the MIF gene and its subsequent soluble levels with the susceptibility of SCC in western Mexican population. This study included 175 SCC patients and 175 age-sex-matched individuals as a reference group (RG) from western Mexico. Genomic DNA was extracted from peripheral blood leukocytes. Polymorphisms were genotyped by endpoint PCR and PCR-RFLP, and the determination of MIF serum levels was measured by ELISA. Clinical characteristics were evaluated by a group of dermatologists. Analysis of [-794(CATT)5-8 /-173G>C] MIF gene polymorphisms showed that the 5C (OR = 2.7, p = 0.02) and the 7G (OR = 3.39, p < 0.01) haplotypes are associated with susceptibility in SCC. MIF soluble levels in SCC patients showed a median of 13.93 ng/mL, whereas the reference group showed 6.000 ng/mL. Our findings suggest that 5C and 7G [-794(CATT)5-8 /-173G>C] MIF gene haplotypes are associated with susceptibility to SCC and that SCC patients present increased soluble levels of MIF.

Analysis of Macrophage Migration Inhibitory Factor Genotype in Hemophilia a Patients.

Hemophilia A, an X-linked bleeding disorder, is caused by a complete or partial deficiency in factor VIII. Multiple factors engage in the development and progression of bleeding episodes in hemophilia patients, especially arthropathy. Detection of macrophage migration inhibitory factor (MIF)-173 G/C polymorphism in people with hemophilia A (PWH) and the possible associations between the type of MIF gene polymorphism and selected disease-related variables. This case-control study included 95 male patients with hemophilia A and 95 non-hemophiliac subjects, all aged from 2 months to 63 years. An allele-specific polymerase chain reaction (AS-PCR) with a multiplex technique was used to detect MIF polymorphisms. A significantly higher frequency of GG polymorphism was reported in the control group (81, 85.3%) compared to PWH (64, 67.4%), while a significantly higher frequency of GC polymorphism was found in PWH (21, 22.1%) than that in healthy subjects (10, 10.5%), P < 0.05. The G allele polymorphism was detected in 90.0% of the control group compared to 78.4% of PWH (149 subjects), while the C allele frequency was higher in PWH (41, 21.6%) compared to that in healthy individuals (18, 10.0%), P < 0.05. The frequencies of varied MIF-173 polymorphisms did not show significant differences among patients with different clinical presentations or in relation to presence of inhibitors, P > 0.05. MIF-173 GC polymorphism is seen in PWH more than that in healthy individuals. Further studies are required to detect additional SNPs through sequencing of the MIF gene and to detect MIF serum levels during bleeding episodes.

Macrophage Migration Inhibitory Factor and Gene Polymorphism (rs755622G&gt;C) in Unstable Vitiligo Patients

Vitiligo pathogenesis is related to the macrophage migration inhibitory factor (MIF) protein. This study aimed to assess the lesional MIF levels and gene polymorphisms (rs755622G&gt;C) in patients with vitiligo. To assess the consequences of combining narrow‐band ultraviolet B with oral minipulse prednisolone as opposed to a combination with oral methotrexate on MIF levels in vitiligo patients, 50 unstable vitiligo patients and 50 controls were randomly chosen for comparison. MIF levels in skin homogenates and MIF (rs755622G&gt;C) single nucleotide polymorphisms were assessed using the ELISA and the polymerase chain reaction restriction fragment length polymorphism (RFLP‐PCR) techniques. We found significantly higher lesional MIF levels, a higher frequency of both (GC) and (CC) genotypes, and a significantly more frequent mutant allele (C) in patients than in controls. In addition, there was a significantly lower frequency of the allele (C) among patients who exhibited moderate to marked therapeutic improvement than among those who showed minimal to mild improvement. In conclusion, tissue MIF and gene polymorphisms were associated with vitiligo. In addition, oral corticosteroids, narrow‐band ultraviolet B, methotrexate‐targeted tissue MIF, and gene polymorphisms can improve unstable vitiligo.

Expression Patterns of Macrophage Migration Inhibitory Factor and Its Gene Variants (MIF-173 G˃C) in Verruca Vulgaris.

IntroductionVerruca vulgaris is a benign hyperkeratotic proliferation of the epidermis. Few studies look at the differences in serum and tissue macrophage migration inhibitory factor (MIF) levels in verruca vulgaris, as well as its gene polymorphisms that have yet to be explored. The current study provided in-depth evaluation of MIF in serum and tissues of patients with verruca vulgaris, and establishes for the first time the possible association of MIF gene polymorphisms with common warts.MethodsThis case-control study included 50 patients who were diagnosed clinically as common warts in comparison with 50 age and sex-matched controls. Clinical examination was done on all included cases. Serum MIF was measured using enzyme-linked immunosorbent assay (ELISA), while its tissue expression was analyzed using Western blotting and immunohistochemical techniques for the included participants. Analysis of MIF-173 G˃C single nucleotide polymorphism was performed by polymerase chain reaction (PCR) using restriction fragment length polymorphism (RFLP) technique.ResultsThe overall results revealed significantly lower MIF tissue expression in lesional and perilesional skin biopsies from cases compared to the controls using Western blot and immunohistochemical analysis. Yet, the difference in the serum MIF levels between cases and controls was not significant (p ˃ 0.05). GC genotype of the studied MIF rs755622 G>C SNP could be considered as a protective genetic factor against the occurrence of verruca vulgaris among Egyptians with OR (95% CI) equal 0.444 (0.199–0.989).ConclusionMIF and its genetic variants are thought to play a pathogenic role in verruca vulgaris development and recurrence.

Single-nucleotide polymorphism and haplotype analysis of macrophage migration inhibitory factor gene and its correlation with serum macrophage migration inhibitory factor levels in North Indian psoriatic patients with moderate disease severity: A cross-sectional study.

Psoriasis is associated with significant morbidity and impaired quality of life. Identification of the host genes that influence disease susceptibility and can potentially guide future, targeted therapy is the need of the hour. The aim of the study was to investigate the associations of macrophage migration inhibitory factor (MIF) gene polymorphisms, that is, a 5-8-CATT tetra nucleotide repeats at -794 (-794*CATT5-8) and a single-nucleotide polymorphism at -173 (-173*G/C) with the risk of chronic plaque psoriasis and to observe the correlation, if any, of disease determinants with genetic functional variants and circulating MIF levels. Five hundred and seventeen individuals (265 psoriasis patients and 252 controls) were genotyped for MIF gene polymorphisms. Data were analyzed with respect to disease susceptibility, serum MIF levels, disease severity, age at onset, disease duration and presence of comorbidities. The presence of co-morbidities was more frequently noted in patients with late onset disease (P = 0.01). No statistically significant differences were observed either in genotype (P = 0.680) or allele frequency (P = 0.69) with respect to distribution of MIF-173*G/C polymorphism between patients and controls. The frequencies of genotypes -794*CATT 5/7 and 7/7 were significantly lower in patients (P = 0.027* and 0.038*, respectively). CATT*5/MIF-173*C haplotype occurred at a higher frequency in patients (odds ratio 3.03, 95% confidence intervals 1.09-8.47, P = 0.02). The mean serum MIF levels were significantly higher in patients as compared to controls (P < 0.001). The presence of either extended MIF -794*CATT repeats or C allele did not reveal any significant association with serum MIF levels or age at onset. Analysis of effect of various disease determinants revealed no significant association with genetic variants and serum MIF levels. The lesional expression of MIF could not be studied. Our results showed that CATT*5/MIF-173*C haplotype is associated with increased susceptibility to psoriasis vulgaris.

Association between MIF gene promoter rs755622 and susceptibility to coronary artery disease and inflammatory cytokines in the Chinese Han population

Macrophage migration inhibitory factor (MIF) is an essential mediator of atherosclerotic plaque progression and instability leading to intracoronary thrombosis, therefore contributing to coronary artery disease (CAD). In this study, we investigated the relationship between MIF gene polymorphism and CAD in Chinese Han population. Three single nucleotide polymorphisms (SNP, rs755622, rs1007888 and rs2096525) of MIF gene were genotyped by TaqMan genotyping assay in 1120 control participants and 1176 CAD patients. Coronary angiography was performed in all CAD patients and Gensini score was used to assess the severity of coronary artery lesions. The plasma levels of MIF and other inflammatory mediators were measured by ELISA. The CAD patients had a higher frequency of CC genotype and C allele of rs755622 compared with that in control subjects (CC genotype: 6.5% vs. 3.9%, P = 0.008, C allele: 24.0% vs. 20.6%, P = 0.005). The rs755622 CC genotype was associated with an increased risk of CAD (OR: 1.804, 95%CI: 1.221–2.664, P = 0.003). CAD patients with a variation of rs755622 CC genotype had significantly higher Gensini score compared with patients with GG or CG genotype (all P < 0.05). In addition, the circulating MIF level was highest in CAD patients carrying rs755622 CC genotype (40.7 ± 4.2 ng/mL) and then followed by GC (37.9 ± 3.4 ng/mL) or GG genotype (36.9 ± 3.7 ng/mL, all P < 0.01). Our study showed an essential relationship between the MIF gene rs755622 variation and CAD in Chinese Han population. Individuals who carrying MIF gene rs755622 CC genotype were more susceptible to CAD and had more severe coronary artery lesion. This variation also had a potential influence in circulating MIF levels.

Haplotypes of (−794(CATT)5–8/−173G>C) MIF gene polymorphisms and its soluble levels in basal cell carcinoma in western Mexican population

Basal cell carcinoma (BCC) is the most common dermatological neoplasms in Caucasian populations. In Mexico, a prevalence of 3.9 per 1000 habitants is estimated. Recently, the macrophage migration inhibitory factor...

The Macrophage Migration Inhibitory Factor (MIF) Promoter Polymorphisms (rs3063368, rs755622) Predict Acute Kidney Injury and Death after Cardiac Surgery.

Background: Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT5–7 (rs5844572/rs3063368,“-794”) and G>C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. Methods: In 1116 patients undergoing cardiac surgery, the MIF gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Results: Patients with at least one extended repeat allele (CATT7) had a significantly higher risk of acute kidney injury (AKI) compared to others (23% vs. 13%; OR 2.01 (1.40–2.88), p = 0.0001). Carriers of CATT7 were also at higher risk of death (1.8% vs. 0.4%; OR 5.12 (0.99–33.14), p = 0.026). The GC genotype was associated with AKI (20% vs. GG/CC:13%, OR 1.71 (1.20–2.43), p = 0.003). Multivariate analyses identified CATT7 predictive for AKI (OR 2.13 (1.46–3.09), p < 0.001) and death (OR 5.58 (1.29–24.04), p = 0.021). CATT7 was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, p = 0.008). Conclusion: The CATT7 allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance.

MIF gene rs755622 polymorphism positively associated with acute coronary syndrome in Chinese Han population: case\u2013control study

Macrophage migration inhibitory factor (MIF) has been recognized as a major player in the pathogenesis of atherosclerosis. This study determined the association between polymorphisms of MIF gene and acute coronary syndrome (ACS). The polymorphism of MIF gene (rs755622, rs1007888 and rs2096525) was analyzed in 1153 healthy controls and 699 ACS cases in Chinese Han population. Plasma MIF level was also measured in part of ACS patients (139/19.9%) and healthy controls (129/11.2%) randomly. Most participants including healthy controls and ACS patients carried rs755622 GG (63.1% vs. 56.7%) and CG genotypes (33.1% vs. 38.9%) and G allele of rs755622 (79.6% vs. 76.1%, respectively), while CC genotype (3.8% vs. 4.4%) and C allele (20.4% vs. 23.9%) carriers were the lowest. Multivariate logistic regression analysis showed that carriers with rs755622 C allele had a higher risk of ACS compared to other genotypes (AOR = 1.278, 95% CI: 1.042–1.567). In addition, CC genotype carriers had the highest plasma levels of MIF than other genotype carriers. The MIF level in ACS patients with CC genotype was significantly higher than ACS patients carrying GG genotype and healthy controls carrying 3 different genotypes of MIF gene rs755622. Our findings indicate that MIF gene rs755622 variant C allele is associated with increased risk of ACS. Identification of this MIF gene polymorphism may help for predicting the risk of ACS.

Protective role of macrophage migration inhibitory factor −173 G > C (rs755622) gene polymorphism in pediatric patients with dilated cardiomyopathy

BackgroundThe last decades have witnessed expanding evidence corroborating the major role of numerous cytokines involved in the pro-inflammatory and immunomodulatory responses. Macrophage migration inhibitory factor (MIF) may have major impact on the outcome of heart diseases; this pleiotropic cytokine is known to be implicated in myocardial inflammation. Single nucleotide polymorphism (SNP) in the MIF promoter (rs755622) regulates MIF expression and can lead to worse prognosis. The aim of our study was to discuss the possible association between MIF-173 genetic polymorphism and pediatric dilated cardiomyopathy (DCM). MethodsOur study enrolled 105 unrelated individuals (53patients with DCM, and 52age- and sex-matched healthy controls). Genetic polymorphisms of several cytokine genes are known to result in altered gene expression. TaqMan genotyping assay and Polymerase chain restriction fragment length polymorphism (PCR-RFLP) methods were used. ResultsThe overall data showed a significant correlation between MIF gene polymorphism and DCM patients. In codominant model, the frequencies of the GG, GC, and CC genotypes of MIF 173G/C were 54.7%, 34%, and 11.3% in cases and were 22%, 78%, and 0% in controls, respectively. A protective effect was observed under dominant genetic model CC + CG vs. GG (p = 0.0009, OR = 0.2334, 95% CI = 0.0987–0.5518). ConclusionThe results obtained in our analysis provide evidence on the potential protective role that MIF-173G/C play in the development of DCM disease in the pediatric population. MIF 173G/C rs755622 was significantly associated with a reduction in risk of pediatric DCM.

Macrophage migration inhibitory factor polymorphism (rs755622) in alopecia areata: a possible role in disease prevention.

Alopecia areata (AA) is an organ-specific autoimmune disease that targets the bulb of the hair follicles and results in non-scarring hair loss that can range from patchy lesions to involvement of the entire scalp. AA develops when the hair follicles lose their physiologic state of immune privilege. One of the key factors that help in maintaining this immune privilege by suppressing natural killer cells is macrophage migration inhibitory factor (MIF). Surprisingly, MIF is also known to provoke autoimmunity by upregulating cytokines. To address this dilemma and understand the exact nature of the involvement of MIF in disease pathogenesis we investigated the association of MIF gene polymorphisms (-173 G > C, rs755622) with AA by conducting a case-control study of 274 subjects. We observed that the frequency of the C allele in the patients was significantly lower than the control group (0.15, 0.23, respectively, p = 0.01) and the combined frequencies of the CC and GC genotypes (dominant Mendelian pattern) had the most prevalent difference between the two groups (odds ratio 0.60, 95% confidence interval 0.36-0.99; p = 0.048).Since the C allele is associated with higher MIF transcription levels, this could infer that MIF is more likely to attribute to the preservation of the immune privilege rather than acting as a proinflammatory factor.

Increased serum levels and promoter polymorphisms of macrophage migration inhibitory factor in schizophrenia

BackgroundNumerous studies have suggested that an immune system imbalance plays an important role in schizophrenia. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine. It plays multiple roles in various biological processes, including inflammation and neurogenesis. Furthermore, several exhaustive serum proteomic profiling studies have identified MIF as a potential biomarker of schizophrenia. Here, we investigate MIF protein levels in serum and postmortem prefrontal cortex in patients with schizophrenia and controls. Moreover, we investigate the association of two functional polymorphisms in the MIF gene promoter region (MIF-794CATT5–8 microsatellite and MIF-173G/C single-nucleotide polymorphism [SNP]) with schizophrenia. MethodsWe measured serum MIF levels with an enzyme-linked immunosorbent assay (ELISA) (51 patients vs. 86 controls) and postmortem brain MIF levels with a western blotting assay (18 patients vs. 22 controls). Subsequently, we genotyped the MIF-794CATT5–8 microsatellite with a fluorescence-based fragment assay and the MIF-173G/C SNP with a TaqMan SNP genotyping assay (1483 patients vs. 1454 controls). ResultsSerum MIF levels were significantly higher in patients with schizophrenia than in controls (p=0.00118), and were positively correlated with antipsychotic dose (Spearman's r=0.222, p=0.0402). In addition, an earlier age of onset was observed in patients with a high serum MIF level (≥40ng/mL) than those with a low serum MIF level (<40ng/mL) (p=0.0392). However, postmortem brain MIF levels did not differ between patients with schizophrenia and controls. The association study revealed that the CATT6-G haplotype was nominally significantly associated with schizophrenia (p=0.0338), and that the CATT6 allele and CATT6-G haplotype were significantly associated with female adolescent-onset schizophrenia (AsOS) (corrected p=0.0222 and p=0.0147, respectively). ConclusionsThese results suggest that serum MIF level is a potential pharmacodynamic and/or monitoring marker of schizophrenia, and is related to a novel antipsychotic effect beyond dopamine antagonism. Furthermore, the MIF gene polymorphisms are associated with the risk for schizophrenia especially in adolescent females, and are potential stratification markers of schizophrenia. Further studies of MIF are warranted to elucidate the pathophysiology of schizophrenia and the effects of antipsychotics.

Macrophage migration inhibitory factor (MIF) gene -173 G>C polymorphism and its relationship to coronary artery disease and type 2 diabetes

Recent studies indicate that macrophage migration inhibitory factor (MIF) is a potent proinflammatory cytokine which mediates the inflammatory process during atherosclerosis. The purpose of the study was to investigate an association between MIF gene polymorphism and type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) in the Turkish population. A total of 139 unselected Turkish patients with significant CAD (coronary lesion with 50-100% stenosis) and 120 control participants (coronary lesion with <30% stenosis) were genotyped for MIF rs755622 polymorphisms using hybridization probes in a Roche LightCycler 480 Real-Time Polymerase Chain Reaction 480 device. Blood samples were drawn before coronary angiography. Gensini and SYNTAX scores were used to determine the angiographic extent and severity of CAD. When the groups were stratified according to T2DM, polymorphism of MIF was not associated with T2DM in CAD patients (p>0.05). In the same subgroups, carriers of the MIF common allele in the control group demonstrated a protection against developing T2DM compared with noncarriers (p<0.05). In addition, MIF C allele carriage was associated with higher glycated hemoglobin (HbA1c) in the T2DM group (p=0.038). The MIF rs755622 polymorphism was associated with HbA1c. This result suggests that the MIF gene variant may contribute to CAD risk through diabetes in the Turkish population.

Association of macrophage migration inhibitory factor - 173 G/C polymorphism with dilated cardiomyopathy in children

Objective The objective of this study was to detect the relation between macrophage migration inhibitory factor (MIF) −173 G/C gene polymorphism and dilated cardiomyopathy (DCM) in children. Background DCM is the most common cardiomyopathy. Myocardial inflammation is one of the commonest mechanisms in cardiomyopathy. MIF plays an important role in the control of innate immune responses and promotes proinflammatory biological activities; hence, MIF gene polymorphisms may predispose affected hosts to severe inflammatory or infectious disease. Patients and methods This study was conducted on 50 patients, 30 patients with DCM and 20 age-matched and sex-matched healthy controls. All patients were subjected to history taking, clinical examination, echocardiography, and laboratory measurement of serum sodium and uric acid. Patients and controls were subjected to PCR-restriction fragment length polymorphism to determine MIF 173 G/C polymorphism. Results Our study revealed a significant statistical difference in the distribution of the genotypes and allele frequencies between patients and controls. Studying the relation between different genotypes and echocardiographic parameters (ejection fraction, fractional shortening, left ventricular end-diastolic diameter and left ventricular end-systolic diameter) revealed a highly significant difference between different genotypes among patients. With regard to laboratory characteristics, there was a significantly higher serum sodium level in the CC genotype, while the uric acid level showed no significant difference between different genotypes among patients. Conclusion In our study, we conclude that the CC genotype of MIF gene may be a risk factor for cardiomyopathic patients and that the C allele is associated with severe clinical condition.

Associations between circulating macrophage migration inhibitory factor (MIF) levels and rheumatoid arthritis, and between MIF gene polymorphisms and disease susceptibility: a meta-analysis

AimTo systematically review evidence regarding the relationship between circulating macrophage migration inhibitory factor (MIF) levels and rheumatoid arthritis (RA), and the association between MIF gene polymorphisms and RA susceptibility.DesignWe performed...

MBL2 and MIF gene polymorphisms in cardiovascular patients with atherosclerotic lesions undergoing heart valve replacement

ABSTRACTThe basic underlying factor for cardiovascular diseases is atherosclerosis, which is a multifactorial disease driven by environmental and genetic factors. We aimed to study the genetic polymorphism in mannose binding lectin-2 (MBL2) and macrophage migration inhibitory factor (MIF) in the arteries of patients with atherosclerotic lesions who underwent cardiac valve replacement for cardiac valve stenosis. Thirty-five patients (38.9 %) operated with coronary bypass surgery (coronary group, CG), 55 (61.1 %) patients operated with aortic or mitral valve replacement (valve group, VG) and 100 healthy controls were analyzed for codon 54 A/B polymorphism in the MBL2 gene and –173 G/C polymorphism in the MIF gene by using the method of polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The comparison of the healthy control group with CG and VG in terms of the MBL2 genotypes revealed significantly lower AA genotype and A allele ratios. The comparison of the healthy control group with CG and VG in terms of the MIF genotypes showed significantly lower GG genotype and G allele ratios. We suggest that the lower frequency of the GG genotype/G allele of the MIF gene and of the AA genotype/A allele of the MBL2 gene may be associated with the ethiopathogenesis of CG and VG patients.

Macrophage Migration Inhibitory Factor Serves As an Upstream Regulator of NLRP3 Expression and Subsequent IL-1beta Production in Human Monocytes in Response to Lupus U1-snRNP Immune Complex

Abstract The pathologic hallmarks of systemic lupus erythematosus (SLE or lupus) are altered immune responses to nuclear autoantigens with autoantibody production and subsequent tissue injury. TLR7/8 recognize the ssRNA of the self-antigen U1-small nuclear ribonucleorprotein (U1-snRNP) that is targeted by anti-U1-snRNP antibodies (Abs) in lupus. Recently, we showed IL-1β production from human monocytes (MO) exposed to a combination of U1-snRNP and anti-U1-snRNP Abs (snRNP immune complexes) via the NLRP3 inflammasome. Macrophage migration inhibitory factor (MIF), primarily produced from MO and macrophages, promotes the production of IL-1β, IL-6 and TNF-α, which are increased in lupus patients. Data showed an association between serum MIF levels and MIF gene polymorphisms with lupus-related organ damage and decreased glomerulonephritis in lupus-prone mice treated with MIF antagonists. Here we investigated the possible mechanisms underlying the functional link between MIF and the NLRP3 inflammasome. The snRNP immune complexes (ICs) induced high levels of MIF and IL-1β from freshly purified human MO. The small molecule MIF inhibitor MIF098, which interferes the binding of MIF to its receptor complex, decreased the production of IL-1β from MO in response to the snRNP ICs. The inhibitor substantially reduced the expression of NLRP3 and caspase-1 activation. This phenomenon is likely mediated in part by the suppression of NF-kB activation. Plus, exogenous MIF increased IL-1β production by the MO. Our results first show the production of MIF from MO by the lupus snRNP IC and the regulation of the NLRP3 inflammasome by MIF in human, providing a scientific rationale for translating animal studies targeting MIF into human lupus.

MIF Gene Polymorphism rs755622 Is Associated With Coronary Artery Disease and Severity of Coronary Lesions in a Chinese Kazakh Population: A Case-Control Study.

Inflammation plays an important role in the pathogenesis of atherosclerosis. Recent studies indicate that macrophage migration inhibitory factor (MIF) is a potent proinflammatory cytokine which mediates the inflammatory process during atherosclerosis.The polymorphism of MIF gene (rs755622 [−173G/C], rs1007888, and rs2096525) were genotyped by TaqMan single nucleotide polymorphism (SNP) genotyping assay in 320 patients with coronary artery disease (CAD) and 603 controls in a Chinese Kazakh population. Coronary angiography was performed on all CAD patients and Gensini score was used to assess the severity of coronary artery lesions.The frequency of the CC genotype and C allele of rs755622 were significantly higher in CAD patients than that in control subjects (8.4% vs. 5.1%, P < 0.001, 30.3% vs. 22.1%, P < 0.001, respectively). Multivariate logistic regression analysis showed that individuals with CC genotype or C allele had a higher risk for CAD (CC genotype vs. GG genotype, OR = 2.224, 95% CI, 1.239–3.992, P = 0.007, and C allele vs. G allele, OR = 1.473, 95% CI, 1.156–1.876, P = 0.002, respectively). Moreover, CAD patients with rs755622 C allele (CC + CG genotype) have higher levels of Gensini score when compared to C allele noncarriers (32.74 ± 26.66 vs. 21.44 ± 19.40, P < 0.001, adjusted).Our results suggested that the CC genotype and C allele of MIF rs755622 SNP may be a genetic marker for the risk of CAD and potentially predict the severity of CAD in Chinese Kazakh population.

Association between Macrophage Migration Inhibitory Factor Gene Variation and Response to Glucocorticoid Treatment in Sudden Sensorineural Hearing Loss

Several lines of evidence suggest the role of the immune system in the pathogenesis of sudden sensorineural hearing loss (SSNHL). Macrophage migration inhibitory factor (MIF) mediates its role in various immune and inflammatory conditions by the regulation of immune reactions. Several studies have confirmed an association between MIF gene polymorphisms and susceptibility to various inflammatory and autoimmune disorders. The aim of this study was to explore the association between the MIF (-173 G/C) polymorphism (rs755622) and SSNHL in an Iranian population. In this case-control association study, SSNHL cases (n = 77) were included. Normal healthy subjects (n = 100) were also recruited from the same region. Genotyping for MIF (-173 G/C) polymorphism was carried out using the polymerase chain reaction-restriction fragment length polymorphism technique. The frequency of the MIF -173 C allele carriers (GC + CC genotype) was significantly elevated in SSNHL patients who responded to glucocorticoid treatment compared with the patients with no response to treatment. These results suggest that the MIF gene polymorphism is associated with a response to glucocorticoid treatment in patients with SSNHL.