Macrophage Migration Inhibitory Factor Rs755622 Research Articles

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.

The influence of Interleukin-6, Interleukin-8, Interleukin-10, Interleukin-17, TNF-A, MIF, STAT3 on lung cancer risk in Moroccan population

To date, several studies have reported that key cytokines in the inflammatory system have important roles in the pathogenesis of cancer, notably in lung cancer. The aim of this case-control study, conducted for the first time in Moroccan population, was to investigate and to analyze the association of the following inflammatory cytokine genes Interleukin (IL)-6, Interleukin (IL)-8, Interleukin (IL)-10, Interleukin (IL)-17, Tumor Necrosis Factor-Alpha (TNFA), Macrophage migration Inhibitory Factor (MIF) and Signal Transducer and Activator of Transcription 3 (STAT3) with lung cancer risk in our patients. Firstly, the mRNA expression was assessed by a quantitative real time PCR in the peripheral blood of lung cancer patients and healthy subjects. Secondly, polymorphisms in the genes encoding cytokines were assessed in 160 lung cancer patients and 150 healthy controls. Genotyping analysis was performed with a Real-Time polymerase chain reaction using TaqMan® genotyping assays on a 7500 FAST Real-Time PCR System and Restriction Fragment Length PolymorphismPCR. Our results revealed a significant difference in mRNA expression levels of IL-6, IL-8, IL-10, IL-17 and TNFA genes in lung cancer patients compared to healthy subjects (P < 0.05). Among the studied genes, we found a significant association between lung cancer risk in our patients and the following polymorphisms IL-6 (rs1800795, rs1800796), IL-8 (rs4075, rs2227306), IL-17F (rs763780, rs2397084) and MIF (rs755622). In conclusion, the results of our study suggest that IL-6, IL-8, IL-10, IL-17 and MIF cytokine genes may aggravate lung cancer risk in the Moroccan population. However, further investigations are required to confirm our findings.

Association of Vitamin D Receptor Polymorphism (rs2228570, rs1544410, rs7975232, and rs731236) and Macrophage Migration Inhibitory Factor -173 G/C (rs755622) with the Susceptibility of Active Pulmonary Tuberculosis in Makassar, Indonesia

BACKGROUND: The study of Vitamin D Receptor (VDR) and Macrophage Migration Inhibitory Factor (MIF) polymorphisms, associated with active pulmonary tuberculosis (ATB) presents varying results. AIMS: This study aimed to investigate the association between VDR rs2228570, rs1544410, rs7975232, rs731236 and MIF -173 G/C (rs755622) single nucleotide polymorphism (SNP), with susceptibility of developing ATB, and positivity of Interferon Gamma Release Assay (IGRA) results (in household contact). METHODS AND MATERIAL: This study involved 83 ATB and 73 household contacts in Makassar. We checked IGRA based on ELISA in household contacts by using QuantiFERON TB Gold Plus test, and we found that 61.64% (n = 45) of household contacts had positive IGRA. Polymorphism examination was carried out by Sanger sequencing. RESULTS: VDR rs2228570 T/T and T/C-T/T were significantly associated with higher risk of active tuberculosis. VDR rs7975232 G/G genotype was associated with an increased risk of developing active TB compared to T/T-T/G. Haplotype analysis of VDR rs2228570, rs1544410, rs7975232, rs731236 and combination with MIF rs755622 demonstrated that TGGTG was observed to have a higher risk of tuberculosis. CONCLUSIONS: The combination of VDR and MIF variants may contribute to the susceptibility of active tuberculosis disease.

MIF promoter polymorphism increases peripheral blood expression levels, contributing to increased susceptibility and poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. The etiology and pathogenesis of HCC remain unclear. Macrophage migration inhibitory factor (MIF) plays a critical role in the pathogenesis of hepatocellular carcinoma. The association between MIF polymorphisms and its expression level in HCC has rarely been demonstrated. In the present study, the peripheral blood of 202 patients with HCC (HCC group), 242 patients with chronic hepatitis B (CHB group), 215 patients with liver cirrhosis (LC group) and 227 healthy volunteers (normal group) were collected, DNA was extracted and the target fragment of MIF gene was amplified using PCR. The products were then sequenced, and the expression levels of MIF protein were tested using ELISA. The results showed that the MIF rs755622 polymorphism was associated with an increased susceptibility and metastasis of HCC, and that the genotypes GC and CC were associated with poor prognosis of HCC. Compared with the normal, CHB and LC groups, the expression of MIF in the peripheral blood of the HCC group was significantly increased, and the high expression was associated with to poor prognosis. In the HCC group, MIF protein levels for genotypes GC and CC were increased compared with those of genotype GG. The current study indicated that the MIF rs755622 polymorphism is associated with susceptibility and metastasis of HCC, and that the GC and CC genotypes may be indicators of poor prognosis, which may be ascribed to the MIF rs755622 polymorphism leading to elevated MIF protein expression in peripheral blood.

Genetic Variants of the MIF Gene and Susceptibility of Rectal Cancer.

BackgroundRectal cancer (RC) has been documented to be a highly invasive malignant neoplasm worldwide. Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine involved in cell-mediated immunity, immunoregulation, inflammation. In vitro and in vivo studies have identified that MIF was involved in the carcinogenesis and progression of RC.Patients and MethodsThis case–control study evaluated associations of genetic variants of the MIF gene and serum level of MIF with susceptibility of RC.ResultsWe found MIF level was associated with an increased risk of RC (OR for per unit: 1.38, 95% CI:1.32–1.44; P < 0.001). Both MIF rs2012133 (OR = 1.30; 95% CIs = 1.08–1.58; P = 0.007) and rs755622 (OR = 1.45; 95% CIs = 1.15–1.82; P = 0.002) were significantly associated with increased risk of RC. Besides, we also found MIF rs5844572 was significantly associated with increased susceptibility of RC, with OR for per CATT repeat of 1.28 (95% CIs: 1.16–1.41; P < 0.001). Further, we found all three variants of the MIF gene, rs5844572, rs2012133 and rs755622, could increase serum level of MIF.ConclusionThis study suggests that MIF plays an important role in the carcinogenesis of RC and could be used as a biomarker for early detection and prediction of RC.

Functional variants in the promoter region of macrophage migration inhibitory factor rs755622 gene (MIF G173C) among patients with heart failure: Association with echocardiographic indices and disease severity

BackgroundHeart failure (HF) is a serious public health concern resulting in death. An individual predisposition to HF is determined by relationship between genetic and environmental variables. The macrophage migration inhibitory factor (MIF) is a significant mediator that involved in a variety of inflammatory and cardiovascular diseases. To reveal contribution of MIF rs755622 G173C gene variants in the promoter region towards HF pathogenesis and investigate association between recognized genotype and clinical characteristics. Patients and methodsWe recruited 90 patients with HF, 63 with preserved ejection fraction (HFpEF) and 27 with reduced ejection fraction (HFrEF), and 60 age- and sex- matched controls. MIF rs755622 (G>C) single-nucleotide polymorphism was genotyped by PCR-RFLP method. ResultsThe GG genotype of MIF rs755622 gene polymorphism was more frequent in HF patients than in controls which increased the risk of HF by about 4.25 times (p<0.05). The distribution of the GG, GC and CC genotypes of MIF were 42%, 21% and 0.0% among HFrEF, and 33.3%, 55.6% and 11.1% among HFpEF respectively. Higher frequency of MIF rs755622 G allele among HFrEF (100%) compared to HFpEF (88.9%) (p = 0.007). MIF-GG genotype variant had significantly lower LVEF. In multivariate analysis, MIF-GG genotype was independent risk predictor among HF (OR 4.6). ConclusionMIF rs755622 (GG) could be considered as a probable genotypic risk factor for HF, especially in those with HFrEF which increases the possibility that MIF contribute to HF progression. MIF genotype assay may serve as early predictor and help to recognize those at great risk of developing HF.

MIF\xa0-173G/C (rs755622) polymorphism modulates coronary artery disease risk: evidence from a systematic meta-analysis

BackgroundCoronary artery disease (CAD) remains one of the major causes of death in humans. Genetic testing may allow early detection and prevention of this disease. This study aimed to investigate the association between the macrophage migration inhibitory factor (MIF) -173G/C (rs755622) polymorphism and susceptibility to CAD based on a meta-analysis.MethodsWe searched several databases to identify observational case-control studies investigating the association between the MIF -173G > C (rs755622) polymorphism and CAD risk published before July 30, 2019. Data were analyzed using the STATA software.ResultsSix studies, comprising a total of 1172 CAD cases and 1564 controls evaluated for MIF polymorphisms, were included. The occurrence of CAD was found to be associated with the C allele of the MIF rs755622 SNP in the total population (C/G, OR = 1.489, 95% CI = 1.223–1.813). Further, MIF –173G/C polymorphism was significantly associated with CAD under the allelic model in the Asian (C/G, OR = 1.775, 95% CI = 1.365–2.309) and Caucasian (C/G, OR = 1.288, 95% CI 1.003–1.654) subgroups. The data showed that the risk of CAD was higher in the population carrying the C allele.ConclusionsWe found evidence of associations between MIF -173C/G and CAD susceptibility in the Asian and Caucasian populations.

Association of the IL-17A rs2275913 and MIF rs755622 polymorphisms with the risk of gastric and colorectal cancer

BackgroundInterleukin 17 (IL-17) and Macrophage migration inhibitory factor (MIF) are pro-inflammatory cytokines that play an important role in gastric and colorectal cancer pathogenesis. AimThe main objective of our study is to investigate the potential association of IL-17A (−197G > A) rs2275913 and MIF (−173 G > C) rs755622 polymorphisms with susceptibility to gastric and colorectal cancers in Moroccan population. MethodsWe conducted a case-control study that included 70 gastric cancer patients; 70 colorectal cancer patients; and 70 healthy controls. Genotyping was performed with real-time polymerase chain reaction (PCR), using a TaqMan single-nucleotide polymorphism (SNP) genotyping assay. ResultsThe mutant genotype AA of the IL-17 rs2275913 polymorphism was correlated with a higher risk of developing colorectal cancer than the GG and AG genotypes combined [odds ratio (OR) = 2.7284; 95% confidence interval (CI) = 1.6491–4.5141, p = .0001]. The wild type genotype GG of the MIF rs755622 polymorphism has a slight protective effect against colorectal [odds ratio (OR) = 0.1262; 95% confidence interval (CI) = 0.0148–1.0733, p = .0581] and gastric cancer [odds ratio (OR) = 0.0749; 95% confidence interval (CI) = 0.0090–0.6237, p = .0165]. ConclusionThe IL-17A rs2275913 (−197G > A) polymorphism could contribute to the risk of colorectal cancer and may be utilized as a genetic screening marker in assessing colorectal cancer risk in the Moroccan population.

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.

Macrophage Migration Inhibitory Factor (MIF) Gene Promotor Polymorphism Is Associated with Increased Fibrosis in Biliary Atresia Patients, but Not with Disease Susceptibility.

Two polymorphisms, rs755622 and rs5844572, in the promoter region of the macrophage migration inhibitory factor (MIF) gene influence the basal and/or induced transcriptional activity and have been linked to several inflammatory and autoimmune diseases. The aim of this study was to investigate the association between these two polymorphisms and disease susceptibility in patients with biliary atresia (BA). Allele frequencies of rs755622 and rs5844572 were assessed in 60 Egyptian infants with a confirmed diagnosis of BA. DNA was extracted from archival material. For the rs755622, samples were tested using Taqman real-time PCR, and for the rs5844572, samples were tested using fluorescence-based genotyping. The allele frequency in the general population was assessed in 141 healthy adults from the same geographical location. No statistical differences were observed in the allele frequencies of either rs755622 or rs5844572 between BA patients and controls. The homozygous and heterozygous short repeats (5/5, or 5/X) of rs5844572 were observed more frequently (16/28, 57.1%) in BA patients with mild to moderate fibrosis compared with those with marked fibrosis (10/32, 31.3%). The difference was statistically significant (P = 0.032). In conclusion, we observed no association between MIF rs755622 and rs5844572 polymorphisms and susceptibility to BA; however, the rs5844572 could be linked to the rate of progression of the disease and extent of fibrosis.

The increased concentration of macrophage migration inhibitory factor in serum and cerebrospinal fluid of patients with tick-borne encephalitis

BackgroundHost factors determining the clinical presentation of tick-borne encephalitis (TBE) are not fully elucidated. The peripheral inflammatory response to TBE virus is hypothesized to facilitate its entry into central nervous system by disrupting the blood-brain barrier with the involvement of a signaling route including Toll-like receptor 3 (TLR3) and pro-inflammatory cytokines macrophage migration inhibitory factor (MIF), tumor necrosis factor-α (TNFα), and interleukin-1 beta (IL-1β).MethodsConcentrations of MIF, TNFα, and IL-1β were measured with commercial ELISA in serum and cerebrospinal fluid (CSF) from 36 hospitalized TBE patients, 7 patients with non-TBE meningitis, and 6 controls. The CSF albumin quotient (AQ) was used as a marker of blood-brain barrier permeability. Single nucleotide polymorphisms rs3775291, rs5743305 (associated with TLR3 expression), and rs755622 (associated with MIF expression) were assessed in blood samples from 108 TBE patients and 72 non-TBE controls. The data were analyzed with non-parametric tests, and p < 0.05 was considered significant.ResultsThe median serum and CSF concentrations of MIF and IL-1β were significantly increased in TBE group compared to controls. MIF concentration in serum tended to correlate with AQ in TBE, but not in non-TBE meningitis. The serum concentration of TNFα was increased in TBE patients bearing a high-expression TLR3 rs5743305 TT genotype, which also associated with the increased risk of TBE. The low-expression rs3775291 TLR3 genotype TT associated with a prolonged increase of CSF protein concentration. The high-expression MIF rs755622 genotype CC tended to correlate with an increased risk of TBE, and within TBE group, it was associated with a mild presentation.ConclusionsThe results point to the signaling route involving TLR3, MIF, and TNFα being active in TBE virus infection and contributing to the risk of an overt neuroinvasive disease. The same factors may play a protective role intrathecally contributing to the milder course of neuroinfection. This suggests that the individual variability of the risk and clinical presentation of TBE might be traced to the variable peripheral and intrathecal expression of the mediators of the inflammatory response, which in turn associates with the host genetic background.

Association of genetic polymorphisms in MIF with breast cancer risk in Chinese women.

Macrophage migration inhibitory factor (MIF) has been reported to associate with increased cancer risk in several cancers. However, the role of MIF in breast cancer (BC) susceptibility remains unknown. For the first time, we conducted a case-control study to assess the potential association of three common MIF gene variants (rs755622, rs1803976, rs11548059) with BC susceptibility in Chinese women. Total 560 breast cancer patients and 583 age- and sex-matched healthy individuals were recruited from Northwest China, and the DNA was genotyped by Sequenom MassARRAY. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed to estimate the associations. We found that C/G, C/C, and C/G-C/C genotype carriers in MIF rs755622 have a significantly increased risk of BC (C/G vs. G/G: OR=1.36, 95% CI=1.07-1.75, P=0.014; C/C vs. GG: OR=2.01, 95% CI=1.06-3.79, P=0.029; C/G-C/C vs. G/G: OR=1.42 95% CI=1.11-1.80, P=0.004). Further analyses indicate that the BC risk is associated with Ki-67 status, and the rs755622 polymorphism increases breast cancer risk among elder patients (≥49years). There is no association between BC risk and other two polymorphisms (rs1803976 and rs11548059) by overall analysis and stratified analysis. In conclusion, MIF rs755622 polymorphism increases BC susceptibility in Chinese population, especially among elder patients.

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.

Methylenetetrahydrofolate reductase C667T polymorphism is associated with increased risk of coronary artery disease in a Chinese population.

Coronary artery disease (CAD) is a complex disease resulting from a combination of environmental and genetic factors. We hypothesized that polymorphisms in methylenetetrahydrofolate reductase (MTHFR) rs1801133 C/T, matrix metalloproteinases (MMPs)-2, tumour necrosis factor (TNF)-α, macrophage migration inhibitory factor (MIF) rs755622G/C and cyclin D1 (CCND1) rs678653G/C contribute to CAD susceptibility. We examined the association between the five polymorphisms and the risk of CAD in a Chinese population of 435 CAD patients and 480 controls. Genotyping was performed using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI/TOF MS). When the MTHFR rs1801133 CC homozygote genotype was used as the reference group, the TT or CT/TT genotypes were associated with a significantly increased risk for CAD. The CT heterozygote genotype was not associated with the risk for CAD. Logistic regression analyses revealed that MMP-2 rs243865 C/T, TNF-α rs1800629 A/G, MIF rs755622G/C and CCND1 rs678653G/C polymorphisms were not associated with the risk of CAD. These findings suggest that the MTHFR rs1801133 C/T polymorphism is associated with CAD development. Future larger studies with other ethnic populations are required to confirm current findings.

Dual Effect of a Polymorphism in the Macrophage Migration Inhibitory Factor Gene Is Associated with New-Onset Graves Disease in a Taiwanese Chinese Population

Graves disease (GD) is an autoimmune disease. Macrophage migration inhibitory factor (MIF) is a potent cytokine that plays an important role in the regulation of immune responses. Two polymorphisms in the promoter region of MIF, rs5844572 and rs755622, are known to affect MIF expression. The purpose of this study was to investigate the relationship between polymorphisms in the MIF gene promoter and the severity of GD. A total of 677 individuals, including 481 GD patients and 196 ethnically matched healthy controls, were genotyped to identify differences in the distribution of the MIF polymorphisms rs5844572 and rs755622. Although there were no significant differences in the allele or genotype distributions among patients with different grades of goiter in GD and healthy controls, the distribution of the C allele, especially C/C genotype, of the rs755622 single nucleotide polymorphism (SNP) in MIF, may be as a risk factor for goiter initiation whereas a protector against development of severe goiter in patients with untreated GD (p<0.05). A goiter-developmental model incorporating genetic (MIF SNP rs755622) and environmental risk factors (gender, radioiodine treatment, thyroid gland surgery and vitiligo) significantly increased the prediction accuracy. Further studies are required to address the role of MIF polymorphisms, as well as their association with other candidate genes, in GD.