Evaluation of expression of VDR-associated lncRNAs in COVID-19 patients

Abstract Background Coronavirus disease 2019 (COVID-19) has been shown to cause serious health problems among them is the Acute Respiratory Distress syndrome (ARDS). Vitamin D receptor (VDR) signaling possibly partakes in the pathophysiology of this devastating complication. Methods In the current project, we have appraised expression levels of VDR, CYP27B1 and a number of associated lncRNAs in the circulation of COVID-19 patients versus healthy subjects using real-time PCR method. Results Expression of SNHG6 was considerably lower in COVID-19 patients compared with control subjects (Ratio of mean expression (RME) = 0.22, P value = 7.04E-05) and in both female and male COVID-19 patients compared with sex-matched unaffected individuals (RME = 0.32, P value = 0.04 and RME = 0.16, P value = 0.000679683, respectively). However, its expression was similar among ICU-hospitalized and non-ICU patients. Similarly, expression of SNHG16 was lower in in COVID-19 patients compared with controls (RME = 0.20, P value = 5.94E-05) and in both female and male patients compared with sex-matched controls (RME = 0.32, P value = 0.04 and RME = 0.14, P value = 0.000496435, respectively) with no significant difference among ICU-hospitalized and non-ICU hospitalized patients. Expression of VDR was lower in COVID-19 patients compared with controls (RME = 0.42, P value = 0.04) and in male patients compared with male controls (RME = 0.27, P value = 0.02). Yet, expression of VDR was statistically similar between female subgroups and between ICU-hospitalized and non-ICU hospitalized patients. Expression levels CYP27B, Linc00511 and Linc00346 were similar among COVID-19 patients and healthy subjects or between their subgroups. Significant correlations have been detected between expression levels of VDR, CYP27B and SNHG6, SNHG16, Linc00511 and Linc00346 lncRNAs both among COVID-19 patients and among healthy controls with the most significant ones being SNHG6 and SNHG16 (r = 0.74, P value = 3.26e-17 and r = 0.81, P = 1.54e-22, respectively). Conclusion Combination of transcript levels of VDR, CYP27B and SNHG6, SNHG16, Linc00511 and Linc00346 could differentiate patients from controls with AUC = 0.76, sensitivity = 0.62 and specificity = 0.81. The current data potentiate SNHG6, SNHG16 and VDR as possible contributors in COVID-19 infection but not in the severity of ARDS.

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Over-expression of IL-6 coding gene in the peripheral blood of migraine with aura patients

Human Antibodies ◽

10.3233/hab-210442 ◽

2021 ◽

pp. 1-5

Author(s):

Mahdi Ramezani ◽

Alireza Komaki ◽

Mohammad Mahdi Eftekharian ◽

Mehrdokht Mazdeh ◽

Soudeh Ghafouri-Fard

Keyword(s):

Migraine With Aura ◽

Peripheral Blood ◽

Healthy Subjects ◽

Migraine Without Aura ◽

P Value ◽

Healthy Controls ◽

Over Expression ◽

Significant Difference ◽

Male Patients ◽

Years Lived With Disability

Migraine is a common disorder which is placed among the top ten reasons of years lived with disability. Cytokines are among the molecules that contribute in the pathophysiology of migraine. In the current study, we evaluated expression levels of IL-6 coding gene in the peripheral blood of 120 migraine patients (54 migraine without aura and 66 migraine with aura patients) and 40 healthy subjects. No significant difference was detected in expression of IL-6 between total migraine patients and healthy controls (Posterior beta = 0.253, P value = 0.199). The interaction effect between gender and group was significant (Posterior beta =-1.274, P value = 0.011), therefore, we conducted subgroup analysis within gender group. Such analysis revealed that while expression of this gene is not different between male patients and male controls (Posterior beta =-0.371, P value > 0.999), it was significantly over-expressed in female patients compared with female controls (Posterior beta = 0.86, P= 0.002). Expression of IL-6 was significantly higher in patients with aura compared with controls (Posterior beta = 0.63, adjusted P value = 0.019). However, expression of this cytokine coding gene was not different between patients without aura and healthy subjects (Posterior beta = 0.193, adjusted P value = 0.281). Therefore, IL-6 might be involved in the pathophysiology of migraine among females and migraine with aura among both sexes.

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Altered Transcript Levels of Cytokines in COVID-19 Patients

10.21203/rs.3.rs-126215/v1 ◽

2020 ◽

Author(s):

Majid Samsami ◽

Alireza Fatemi ◽

Reza Jalili Khoshnoud ◽

Karim Kohansal ◽

Arezou Sayad ◽

...

Keyword(s):

Demographic Data ◽

P Value ◽

Healthy Controls ◽

Cytokine Storm ◽

Related Disorder ◽

Transcript Levels ◽

Expression Levels ◽

Male Patients ◽

Diagnostic Power ◽

The Impact

Abstract The pandemic caused by severe acute respiratory syndrome coronavirus 2 and the related disorder i.e. “coronavirus disease 2019” (COVID-19) have encouraged researchers to unravel the molecular mechanism of disease severity. Several lines of evidence support the impact of "cytokine storm" in the pathogenesis of severe forms of the disorder. We aimed to assess the expression levels of nine cytokine coding in COVID-19 patients admitted in a hospital. Expression levels of IFN-G, IL-2, IL-4, IL-6, IL-17, TGF-B, IL-8 and IL-1B were significantly higher in COVID-19 patients compared with healthy controls and in both female and male patients compared with sex-matched controls. However, expression of none of these cytokines was different between ICU-admitted patients and other patients except for IL-6 whose expression was lower in the former group compared with the latter (ratio of means = 0.33, P value = 4.82E-02). Expression of TNF-A was not different between COVID-19 patients and healthy controls. Then, we assessed diagnostic power of cytokine coding genes in differentiating between COVID-19 patients and controls. The area under curve (AUC) values range from 0.94 for IFN-G to 1.0 for IL-2 and IL-1B. After combining the transcript levels of all cytokines, AUC, sensitivity and specificity values reached 1.0, 1.0 and 0.99, respectively. For differentiation between ICU-admitted patients and other patients, IL-4 with AUC value of 0.68, had the best diagnostic power among cytokine coding genes. Expression of none of cytokine coding genes was correlated with the assessed clinical/demographic data including age, gender, ICU admission, or CRP/ESR levels. Our study provides further evidence for contribution of “cytokine storm” in the pathobiology of moderate/severe forms of COVID-19.

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Seroprevalence of anti-SARS-CoV-2 IgG antibodies in hospitalized patients at a tertiary referral center in North India (Preprint)

10.2196/preprints.23937 ◽

2020 ◽

Author(s):

Dr. Animesh Ray ◽

Dr. Komal Singh ◽

Souvick Chattopadhyay ◽

Farha Mehdi ◽

Dr. Gaurav Batra ◽

...

Keyword(s):

Tertiary Care ◽

Age Groups ◽

Hospitalized Patients ◽

North India ◽

P Value ◽

Care Hospital ◽

Igg Antibodies ◽

Igg Antibody ◽

Increased Risk ◽

Significant Difference

BACKGROUND Seroprevalence of IgG antibodies against SARS-CoV-2 is an important tool to estimate the true extent of infection in a population. However, seroprevalence studies have been scarce in South East Asia including India, which, as of now, carries the third largest burden of confirmed cases in the world. The present study aimed to estimate the seroprevalence of anti-SARS-CoV-2 IgG antibody among hospitalized patients at one of the largest government hospital in India OBJECTIVE The primary objective of this study is to estimate the seroprevalence of SARS-CoV-2 antibody among patients admitted to the Medicine ward and ICU METHODS This cross-sectional study, conducted at a tertiary care hospital in North India, recruited consecutive patients who were negative for SARS-CoV-2 by RT-PCR or CB-NAAT. Anti-SARS-CoV-2 IgG antibody levels targeting recombinant spike receptor-binding domain (RBD) protein of SARS CoV-2 were estimated in serum sample by the ELISA method RESULTS A total of 212 hospitalized patients were recruited in the study with mean age (±SD) of 41.2 (±15.4) years and 55% male population. Positive serology against SARS CoV-2 was detected in 19.8%patients(95% CI 14.7-25.8). Residency in Delhi conferred a higher frequency of seropositivity 26.5% (95% CI 19.3-34.7) as compared to that of other states 8% (95% CI 3.0-16.4) with p-value 0.001. No particular age groups or socio-economic strata showed a higher proportion of seropositivity CONCLUSIONS Around, one-fifth of hospitalized patients, who were not diagnosed with COVID-19 before, demonstrated seropositivity against SARS-CoV-2. While there was no significant difference in the different age groups and socio-economic classes; residence in Delhi was associated with increased risk (relative risk of 3.62, 95% CI 1.59-8.21)

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Low Level of Serum Sclerostin in Adult Patients with Tumor-induced Osteomalacia Comparing with X-linked Hypophosphatemia

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab579 ◽

2021 ◽

Author(s):

Xiaolin Ni ◽

Qi Zhang ◽

Xiang Li ◽

Qianqian Pang ◽

Yiyi Gong ◽

...

Keyword(s):

Bone Mass ◽

Cross Sectional Study ◽

Healthy Controls ◽

Cross Sectional ◽

Significant Difference ◽

Healthy Control ◽

Premenopausal Patients ◽

Male Patients ◽

Sclerostin Level ◽

Sclerostin Antibody

Abstract Context Sclerostin is an inhibitor of Wnt-β-catenin signaling to regulate bone formation. Circulating sclerostin levels were reported to be elevated in patients with X-linked hypophosphatemia (XLH), and sclerostin antibody (Scl-Ab) has been shown to increase bone mass and normalize circulating phosphate levels in Hyp mice. However, circulating sclerostin level in acquired hypophosphatemic patients with tumor-induced osteomalacia (TIO) remains rare reported. Objectives This study was designed to evaluate serum sclerostin levels in TIO patients comparing them with age-, sex- matched healthy controls and XLH patients, and analyze correlation of circulating sclerostin with BMD and laboratory parameters. Design, Setting and Participants 190 individuals including 83 adult TIO patients, 83 adult healthy controls and 24 adult XLH patients were enrolled in this cross-sectional study. Main outcome measures Serum sclerostin levels were determined in TIO patients, healthy controls and XLH patients. Results TIO patients (43 male and 40 female) aged 44.3 ± 8.7 (mean ± SD) years had lower levels of circulating sclerostin than healthy controls (94.2 ± 45.8 vs 108.4 ± 42.3 pg/mL, p = 0.01) with adjustment for age, gender, BMI and diabetes rate. Sclerostin levels were positively associated with age (r = 0.238, p = 0.030). Male patients had higher sclerostin level than female patients (104.7 ± 47.3 vs 83.0 ± 41.8 pg/mL, p = 0.014) and postmenopausal patients had higher tendency of sclerostin level than premenopausal patients (98.4 ± 48.8 vs 71.6 ± 32.3 ng/ml, p = 0.05). Sclerostin levels were positively associated with BMD of L1-4 (r = 0.255, p = 0.028), femoral neck (r = 0.242, p = 0.039) and serum calcium (r = 0.231, p = 0.043). TIO subgroup patients (n=24, 35.9 ± 7.3 years old) comparing with age-, sex-matched adult XLH patients and healthy controls revealed significant difference of sclerostin levels (XLH, TIO and healthy control were 132.0 ± 68.8, 68.4 ± 31.3 and 98.6 ± 41.1 pg/mL, respectively, p < 0.001). Conclusions Circulating sclerostin levels were decreased in TIO patients but increased in XLH patients, which might be result of histological abnormality and bone mass.

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MO477SERUM C-REACTIVE PROTEIN AND PROCALCITONIN LEVELS IN HEMODIALYSIS AND INTRADIALYTIC ALTERATIONS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab090.0039 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Makrouhi Sonikian ◽

Aggeliki Barbatsi ◽

Eugenia Karakou ◽

Theodoros Chiras ◽

Jacob Skarakis ◽

...

Keyword(s):

Healthy Subjects ◽

Control Group ◽

Healthy Controls ◽

C Reactive Protein ◽

Polysulfone Membrane ◽

Reactive Protein ◽

Markers Of Inflammation ◽

Dialysate Flow Rate ◽

Significant Difference ◽

Serum Crp

Abstract Introduction C-reactive protein (CRP) and procalcitonin (PCT) are widely used as markers of inflammation and infection in general population and in chronic hemodialysis (HD) as well. However, in dialysis (D) patients, serum CRP and PCT levels may be elevated even in the absence of inflammatory or infectious disease and diagnostic process is a challenge in such cases. We studied HD patients' laboratory profile concerning CRP and PCT. Subjects and Methods We studied 25 stable HD patients, M/F=22/3, aged 68(44-89) years, dialyzed thrice weekly for 55(6-274) months with a dialysate flow rate of 700 ml/min, with a residual daily diuresis less than 200 ml, Kt/V values of 1,44±0,3 and no signs of infection. Patients were classified in two groups. Group A included 10 patients on pre-dilution online hemodiafiltration (HDF). Group B consisted of 15 patients on conventional HD with low-flux polysulfone membrane. Twenty healthy subjects formed a control group C. Serum CRP and PCT levels were measured in duplicate in A and B groups before and at the end of mid-week dialysis sessions and also in C group. Results Pre-D serum CRP values in the total of patients were higher than those in healthy controls (10,89±19,29 vs 2,54±1,28 mg/L-p=0,004). Compared with group C, pre-D CRP values were higher only in B group (15,98±24,54 mg/L-p=0,001) but not in A group (4,09±3,33 mg/L-p=NS). There was a significant difference in pre-D serum CRP values between A and B groups (p=0,028). At the end of D session serum CRP values showed a tendency to increase in both groups A (5,16±4,81 mg/L) and B (17,00±27,00 mg/L) but differences were not significant. Pre-D serum PCT values in the total of patients were higher than those in healthy controls (0,82±0,9 vs 0,29±0,55 ng/ml-p<0,001). Compared with group C, pre-D PCT values were higher in both A group (0,52±0,15 ng/ml-p<0,001) and B group (1,01±1,13 ng/ml-p=0,006). There was no significant difference in pre-D serum PCT values between A and B groups (p=0,261). At the end of D session serum PCT values decreased in A group (0,32±0,11 ng/ml-p<0,001) and increased in B group (1,12±1,21 ng/ml-p=0,014). Conclusions In patients on both conventional low-flux HD and online HDF pre-D serum CRP and PCT levels were higher than those in healthy subjects. Dialysis modality and membrane flux did not affect post-D serum CRP values, but post-PCT values decreased in online HDF. PCT usefulness might be limited in dialysis with high-flux membranes. Cut-off values have to be established for both markers to eliminate confusion in diagnosis of inflammatory and infectious diseases in hemodialyzed patients.

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Serum potassium disorders predict subsequent kidney injury: a retrospective observational cohort study of hospitalized patients

Kidney & Blood Pressure Research ◽

10.1159/000521833 ◽

2022 ◽

Author(s):

Gianmarco Lombardi ◽

Giovanni Gambaro ◽

Pietro Manuel Ferraro

Keyword(s):

Cohort Study ◽

Serum Potassium ◽

Hospital Admissions ◽

Kidney Injury ◽

Observational Cohort Study ◽

Hospitalized Patients ◽

P Value ◽

Significant Difference ◽

Observational Cohort ◽

Retrospective Observational Cohort Study

Introduction Electrolytes disorders are common findings in kidney diseases and might represent a useful biomarker preceding kidney injury. Serum potassium [K+] imbalance is still poorly investigated for association with acute kidney injury (AKI) and most evidence come from intensive care units (ICU). The aim of our study was to comprehensively investigate this association in a large, unselected cohort of hospitalized patients. Methods: We performed a retrospective observational cohort study on the inpatient population admitted to Fondazione Policlinico Universitario A. Gemelli IRCCS between January 1, 2010 and December 31, 2014 with inclusion of adult patients with at least 2 [K+] and 3 serum creatinine (sCr) measurements who did not develop AKI during an initial 10-day window. The outcome of interest was in-hospital AKI. The exposures of interest were [K+] fluctuations and hypo (HoK) and hyperkalemia (HerK). [K+] variability was evaluated using the coefficient of variation (CV). Cox proportional hazards regression models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs) of the association between the exposures of interest and development of AKI. Results: 21,830 hospital admissions from 18,836 patients were included in our study. During a median follow-up of 5 (interquartile range [IQR] 7) days, AKI was observed in 555 hospital admissions (2.9%); median time for AKI development was 5 (IQR 7) days. Higher [K+] variability was independently associated with increased risk of AKI with a statistically significant linear trend across groups (p-value = 0.012). A significantly higher incidence of AKI was documented in patients with HerK compared with normokalemia. No statistically significant difference was observed between HoK and HerK (p-value = 0.92). Conclusion: [K+] abnormalities including fluctuations even within the normal range are associated with development of AKI.

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MON-LB82 Plasma Expression Level of MiRNA -21 Is Related With the Presence of Papillary Thyroid Cancer

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2132 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Birute Zilaitiene ◽

Aiste Kondrotiene ◽

Daina Pamedytyte ◽

Vaida Simanaviciene ◽

Dalia Dauksiene ◽

...

Keyword(s):

Thyroid Cancer ◽

Healthy Volunteers ◽

Papillary Thyroid Cancer ◽

Diagnostic Value ◽

Healthy Controls ◽

Papillary Thyroid ◽

Expression Levels ◽

Significant Difference ◽

Baseline Levels ◽

Benign Nodules

Abstract Introduction.: There is no effective and reliable biomarker to distinguish benign thyroid nodules (BTN) from papillary thyroid carcinomas (PTC). In this study we analyzed a set of four miRNA molecules in plasma of patients with papillary thyroid cancer, benign nodules and healthy controls to identify miRNA molecules that may be markers of PTC.Aim.: We aimed to investigate the dysregulation of plasma miRNAs in PTC and evaluate the diagnostic value for differentiation of PTC from BTN. Methods.: The expression levels of 4 miRNAs (miR-221, miR-222, miR-146b, miR-21) were measured in 48 PTC patients before thyroidectomy and again after thyroidectomy in a subgroup of 36 patients. Preoperative and postoperative plasma miRNA expression levels were compared with baseline levels established in plasma from the heathy controls group (N=57) and patients with BTN (N=22). MicroRNA-222 and miR-146b, miR-221, miR-21 were included in a panel because they all reportedly were overexpressed in PTC compared to benign nodules or normal thyroid tissue.Results.: Compared with baseline levels in the healthy controls group, miR-221, miR-222, miR-146b, miR-21 levels were significantly higher in the preoperative PTC group (P <0.0001, P=0.002, P=0.028, P =0.021, respectively). A significant reduction in miR-21 expression was observed in postoperative PTC patients. MiR-21 decreased by 5.98-fold (P=0.046) in post- operative samples compared with preoperative samples in the PTC patients.In comparison MiRNRs expression levels in BTN group with healthy controls, miR-221, miR-21 expression levels were significantly higher in the BTN group (P=0.003, P=0.048, respectively). No significant difference was observed between the preoperative PTC group and the preoperative BTN group with regard to the expression of these four miRNA’s. Conclusions: The expression levels of miR-222, miR-146b in plasma were significantly higher in patients who had PTC than in healthy volunteers, whereas levels of miR-221, miR-21 in plasma were significantly higher in patients who had either PTC or BTN before thyroidectomy than in healthy volunteers. Furthermore, miR-21 showed a significant reduction of expression levels after thyroidectomy in PTC patients. However, value of these four miRNAs is still limited in differential diagnosis of PTC and benign nodules.

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Evaluation of Putative Type II Toxin-Antitoxin Systems and Lon Protease Expression in Shigella flexneri Following Infection of Caco-2 Cells

Archives of Clinical Infectious Diseases ◽

10.5812/archcid.98625 ◽

2020 ◽

Vol 15 (3) ◽

Author(s):

Erfan Kheradmand ◽

Shabnam Razavi ◽

Malihe Talebi ◽

Mahmood Jamshidian

Keyword(s):

Cell Line ◽

Post Infection ◽

Shigella Flexneri ◽

Fold Increase ◽

Expression Level ◽

Bacterial Invasion ◽

P Value ◽

Lon Protease ◽

Expression Levels ◽

Pcr Method

: Shigella flexneri causes bacillary dysentery in developing countries. Due to recent reports regarding antimicrobial resistance in human S. flexneri, finding alternative therapeutics is of vital importance. Toxin-antitoxin (TA) systems have recently been introduced as antimicrobial targets owing to their involvement in bacterial survival in stress conditions and “persister” cell formation. In this study, the presence of four TA loci were studied in S. flexneri ATCC 12022. The presence of genes coding for the identified TA loci and Lon protease were confirmed by the PCR method using specific primers. Caco-2 cell lines were then infected with this standard strain, and 8 and 24 h post-infection, expression levels of genes coding for the studied TA loci, and Lon protease were evaluated using a real-time PCR method. Expression of mazF, GNAT (Gcn5-related N-acetyltransferase), yeeU, pfam13975, and Lon genes showed 5.4, 9.8, 2.3, 2.7, and 13.8-fold increase, respectively, 8 h after bacterial invasion of the Caco-2 cell line. In addition, the expression of the aforementioned genes showed 4.8, 10.8, 2.3, 3.7, and 16.8-fold increase after 24 h. The GNAT and lon genes showed significantly higher expression levels compared to the control (P value < 0.05). However, the increase in the expression level of yeeU was the same at 8 h and 24 h post-infection. In addition, mazF expression level showed a slight decrease at 24 h compared to 8h post-infection. Genes coding for GNAT and Lon protease showed a significantly higher expression after invading the Caco-2 cell line. Therefore, targeting GNAT or Lon protease can be taken into consideration for finding novel antimicrobial drug strategies. The exact functions and mechanisms of TA systems in S. flexneri isolates are suggested to be experimentally determined.

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Effect of a Persian metabolic diet on the functional dyspepsia symptoms in patients with postprandial distress syndrome: a randomized, double-blind clinical trial

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2021-0368 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Fereshteh Nouri ◽

Mohsen Naseri ◽

Saeed Abdi ◽

Soghrat Faghihzadeh ◽

Mehdi Pasalar ◽

...

Keyword(s):

Clinical Trial ◽

Distress Syndrome ◽

P Value ◽

Intervention Period ◽

Dietary Regimen ◽

Postprandial Distress Syndrome ◽

Severity Scores ◽

Significant Difference ◽

Persian Medicine

Abstract Objectives Postprandial distress syndrome (PDS) is associated with food indigestion. Efficacy of drugs used against PDS is limited whereas dietary modifications were shown to have important beneficial effects. Traditional Persian Medicine (TPM) sages suggested a dietary regimen known as Persian metabolic diet (PMD) for the management of PDS patients. In this study, the efficacy of PMD in alleviating the symptoms of PDS was explored. Methods This single-center, parallel-group, randomized clinical trial included 56 patients whom were randomly allocated to PMD group (29 participants) and Optional diet (OD) group (27 participants). They were instructed to follow the protocol for two weeks. Using a standard validated questionnaire, all outcomes were evaluated at baseline, end of the intervention period, and end of follow-up time. Results At the end of the intervention period, comparing the changes of severity scores between the groups showed a statistically significant difference in week 2 (p-value<0.001) and week 8 (p-value<0.001) follow-up comparing to the baseline. Similarly, at the end of the follow-up period, epigastric fullness, epigastric discomfort, and bloating were significantly improved in the PMD group (p<0.001). Conclusions This diet prepared based on Persian medicine seems to be effective in relieving the symptoms of patients with PDS.

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Expression Analysis of SOCS Genes in Migraine

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.725048 ◽

2021 ◽

Vol 14 ◽

Author(s):

Soudeh Ghafouri-Fard ◽

Kasra Honarmand Tamizkar ◽

Arezou Sayad ◽

Mohammad Taheri ◽

Mohammad Samadian

Keyword(s):

Expression Analysis ◽

Healthy Subjects ◽

Venous Blood ◽

The Other ◽

Cytokine Signaling ◽

Suppressor Of Cytokine Signaling ◽

Expression Levels ◽

Neurological Condition ◽

Male Patients

Migraine is a complex neurological condition affecting a large proportion of persons. Dysregulation of several immune-related transcripts has been noted in migraineurs suggesting an immune-based background for this condition. We measured expression levels suppressor of cytokine signaling (SOCS) genes in the venous blood of migraineurs compared with controls. SOCS1 was down-regulated in patients without aura compared with controls [Ratio of mean expression (RME) = 0.08, P value < 0.001]. This pattern was also detected among female subgroups (RME = 0.06, P value = 0.010), but not among male subgroups (RME = 0.22, P value = 0.114). Expression of SOCS1 was significantly higher in patients with aura compared with those without aura (RME = 5.89, P value = 0.037). Meanwhile, expression of SOCS2 was lower in migraineurs with aura compared with controls (RME = 0.03, P value < 0.001). In addition, this gene was under-expressed in patients without aura compared with controls and in both sex-based subgroups of this group of patients (RME = 0.01, P value < 0.001 for all comparisons). However, its expression was higher in male patients with aura compared with those without aura (P value < 0.001). For SOCS3, we detected a lower level of expression in patients without aura compared with controls (RME = 0.07, P value < 0.001). However, the expression of SOCS3 was higher in patients with aura compared with those without aura (RME = 7.46, P value = 0.001). SOCS5 was down-regulated in patients without aura compared with controls (RME = 0.10, P value < 0.001). Expression of this gene was also lower in patients with aura compared with controls (RME = 0.03, P value < 0.001), and in male patients of this group compared with controls (RME = 0.03, P value = 0.004). On the other hand, expression of SOCS5 was higher in male patients with aura compared with sex-matched patients without aura (RME = 6.67, P value = 0.001). SOCS2 levels could appropriately differentiate migraineurs from healthy subjects. The current study suggests the role of SOCS genes in the pathoetiology of migraine.

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