Protein Cytokines, Cytokine Gene Polymorphisms, and Potential Acute Coronary Syndrome Symptoms

The purpose of this study was to determine whether relationships exist among protein cytokines, cytokine gene polymorphisms, and symptoms of potential acute coronary syndrome (ACS). Participants included 438 patients presenting to the emergency department (ED) whose symptoms triggered a cardiac evaluation (206 ruled in and 232 ruled out for ACS). Presence or absence of 13 symptoms was recorded upon arrival. Levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-18 were measured for all patients. A pilot analysis of 85 patients (ACS = 49; non-ACS = 36) genotyped eight single-nucleotide polymorphisms (SNPs; four TNF and four IL6 SNPs). Logistic regression models were tested to determine whether cytokines or SNPs predicted symptoms. Increased levels of TNF-α and IL-6 were associated with a decreased likelihood of chest discomfort for all patients. Increased levels of IL-6 were associated with a lower likelihood of chest discomfort and chest pressure for ACS patients, and an increased likelihood of shoulder and upper back pain for non-ACS patients. Elevated IL-18 was associated with an increased likelihood of sweating in patients with ACS. Of the four TNF SNPs, three were associated with shortness of breath, lightheadedness, unusual fatigue, and arm pain. In all, protein cytokines and TNF polymorphisms were associated with 11 of 13 symptoms assessed. Future studies are needed to determine the predictive ability of cytokines and related SNPs for a diagnosis of ACS or to determine whether biomarkers can identify patients with specific symptom clusters.

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Cytokine Gene Polymorphisms in the Susceptibility to Acute Coronary Syndrome

Genetic Testing and Molecular Biomarkers ◽

10.1089/gtmb.2011.0182 ◽

2012 ◽

Vol 16 (5) ◽

pp. 359-365 ◽

Cited By ~ 20

Author(s):

Baddela M.V. Srikanth Babu ◽

Bhomireddy Pulla Reddy ◽

Vanacherla Hari Sai Priya ◽

Anjana Munshi ◽

Hanmathrao Surekha Rani ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Gene Polymorphisms ◽

Cytokine Gene ◽

Coronary Syndrome ◽

Cytokine Gene Polymorphisms

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Abstract 18710: Added Value of Electrocardiographic Signs and Symptoms to Improve Early Detection of Acute Coronary Syndrome in the Emergency Department

Circulation ◽

10.1161/circ.132.suppl_3.18710 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Jessica K Zègre-Hemsey ◽

Larisa A Burke ◽

Holli A DeVon

Keyword(s):

Myocardial Infarction ◽

Acute Coronary Syndrome ◽

Signs And Symptoms ◽

Symptom Distress ◽

St Elevation Myocardial Infarction ◽

Specific Symptom ◽

Arm Pain ◽

Coronary Syndrome ◽

Cardiac Symptoms ◽

St Elevation

Background: Early identification and diagnosis are critical in the management of patients with acute coronary syndrome (ACS) since time-dependent therapies reduce patient mortality and morbidity. Objective: The aims of this study were to describe differences in presenting symptoms by individual ACS diagnoses and determine the prognostic value of both signs (electrocardiographic evidence of ischemia) and symptoms for an ACS diagnosis. Method: Patients > 21 years old, with any ECG ischemic changes (ST-elevation, ST-depression, T-wave inversion), elevated serum troponin, and ACS symptoms presenting to one of five emergency departments (ED) were eligible for the study. Patients completed the ACS Symptom Checklist, a validated 13-item instrument that measures cardiac symptoms (typical and atypical). Pearson Chi-square tests were used for bivariate analyses and logistic regression was used for multivariate modeling. Results: A total of 1,031 patients (mean age 60 + 14, 62% male, 70% White) were enrolled; 450 (43.7%) were diagnosed with ACS. One hundred eleven (11%) had ST-elevation myocardial infarction (STEMI), 236 (23%) had non-ST elevation myocardial infarction (NSTEMI), 103 (10%) had unstable angina (UA), and 581 (56%) were ruled-out for ACS. Patients with STEMI were more likely to report chest pain, diaphoresis, and higher symptom distress (p<0.05) at presentation than those without. Patients with NSTEMI were more likely to report arm pain and patients with UA were more likely to report lightheadedness (p<0.05). The presence of any chest symptoms (OR 2.24; 95% CI 1.27-3.97), higher symptom distress (OR 1.07; 95% CI 1.0-1.15), and a lower number of symptoms (OR 0.92; 95% CI 0.86-0.98) were independent predictors of an ACS diagnosis (p<0.05). The strongest predictor of an ACS diagnosis was the presence of ECG ischemic changes (OR 4.51, 95% CI 3.20-6.36) adjusting for symptoms, age, gender, heart rate, arrhythmia, and troponin levels (p<0.001). Conclusion: ECG signs of ischemia combined with specific symptom characteristics may enhance timely triage and detection of ACS in the ED. Predictive models that incorporate presenting signs and symptoms should be explored for this vulnerable population.

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Profile of cytokine gene polymorphisms in Iranian multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458506070237 ◽

2007 ◽

Vol 13 (2) ◽

pp. 253-255 ◽

Cited By ~ 21

Author(s):

A Amirzargar ◽

F Khosravi ◽

S Dianat ◽

F Hushmand ◽

P Maryousef ◽

...

Keyword(s):

Multiple Sclerosis ◽

Gene Polymorphisms ◽

Cytokine Gene ◽

Immune Mediated ◽

Tnf Α ◽

Relapsing Remitting ◽

Cytokine Gene Polymorphisms ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis

Background Cytokine gene polymorphisms have been extensively studied in association with different diseases. The role of cytokine gene polymorphisms in multiple sclerosis (MS), as a chronic immune-mediated neurodegenerative disease, has been previously reported. Materials and methods DNA samples were collected from 44 patients with relapsing-remitting multiple sclerosis (RRMS) and 140 unrelated healthy subjects. All participants in this study were matched for ethnicity. Cytokine gene SNPs were determined using the PCR-SSP method. Results and discussion We found no significant differences between MS patients and controls in most of the studied cytokine genes. Remarkable results were obtained for IL-2 GG —330 genotype (P = 0.06), IL-6 C —174 allele (P = 0.06), CG and GG genotypes (P < 0.001), and GG (P = 0.02) and CG (P < 0.001) haplotypes, and TNF-α A —238 allele (P < 0.001), GG (P = 0.003) and GA (P < 0.001) haplotypes. These results suggest that polymorphic variations of these pro-inflammatory cytokines play an important role in susceptibility to MS. Multiple Sclerosis 2007; 13: 253–255. http://msj.sagepub.com

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A Systematic Review and Meta-Analysis on Multiple Cytokine Gene Polymorphisms in the Pathogenesis of Periodontitis

Frontiers in Immunology ◽

10.3389/fimmu.2021.713198 ◽

2022 ◽

Vol 12 ◽

Author(s):

Xin Liu ◽

Hui Li

Keyword(s):

Systematic Review ◽

Publication Bias ◽

Gene Polymorphisms ◽

Inflammatory Responses ◽

Meta Analysis ◽

Cytokine Gene ◽

Protective Function ◽

Tnf Α ◽

Cytokine Gene Polymorphisms ◽

Ifn Γ

AimPeriodontitis is an inflammatory disease that destroys both soft and hard periodontal tissues. However, a complex periodontal cytokine network remains unclear. This systematic review explored multiple cytokine gene polymorphisms in the pathogenesis of periodontitis.Material and MethodsA systematic search was performed using the databases from previous publications, which indicated the association between cytokine polymorphisms and periodontitis pathogenesis. Meta-analysis was conducted using fixed or randomized models to calculate the significance of multiple cytokine polymorphisms. A total of 147 articles were analyzed with polymorphisms in 12 interleukins [Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4 and IL-13), Th17 (IL-1α, IL-1β, IL-6, and IL-17), and Treg cytokines (IL-10 and TGF-β)]. Doi plot was used to probe the occurrence of publication bias.ResultsThe polymorphisms of IL-2 and TNF-α of Th1 cytokine family may be associated with the pathogenesis or the prevention of periodontitis risk, while the polymorphism of IFN-γ is not related to periodontitis risk. The polymorphisms for IL-4 and IL-13 of Th2 cytokine family are not found to be associated with the pathogenesis of periodontitis. For the polymorphisms of the members of Th17 cytokine family, different IL-1α polymorphisms may have inverse actions in the pathogenesis of periodontitis. IL-1β is a noteworthy cytokine biomarker in periodontitis development and progression. IL-6 may have a protective function in the inflammatory responses of periodontitis, and IL-17 has a weak relationship the inflammatory responses. The polymorphisms for the members of Treg cell cytokines may have a protective function against periodontitis risk. LFK indexes show the major asymmetry due to publication bias.ConclusionIL-1β is a notable cytokine biomarker in periodontitis risk. Treg cytokines favor an anti-inflammatory and protective environment. Further data are needed to confirm the present conclusion due to publication bias.

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Associations between Inflammatory Cytokine Gene Polymorphisms and Susceptibilities to Intracranial Aneurysm in Chinese Population

BioMed Research International ◽

10.1155/2021/8865601 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Lu Xu ◽

Liming Hu ◽

Chongyu Hu ◽

Junyu Liu ◽

Bingyang Li ◽

...

Keyword(s):

Intracranial Aneurysm ◽

Gene Polymorphisms ◽

Chinese Population ◽

Inflammatory Cytokine ◽

Additive Models ◽

Dominant Model ◽

Cytokine Gene ◽

Han Ethnicity ◽

Tnf Α ◽

Cytokine Gene Polymorphisms

Intracranial aneurysm (IA) is a complex disease caused by genetic and environmental factors. Evidence indicates that inflammation plays an important role in IA occurrence. We aimed to explore the associations between inflammatory cytokine gene polymorphisms and IA in a Chinese population. This study enrolled 768 participants of Han ethnicity, including 384 patients with IA and 384 healthy individuals. Sixteen single nucleotide polymorphisms (SNPs) of IL1, IL6, IL12, and TNF-α genes were genotyped using the Sequenom MassARRAY platform. Univariate and multivariate logistic regression analyses were used to analyze the associations. We found IL12B rs3181216 was significantly associated with IA in the recessive and additive models ( OR = 0.46 , 95% CI = 0.23–0.89, P = 0.022 ; OR = 0.74 , 95% CI = 0.56–0.98, P = 0.034 , respectively). TNF-α rs1799964 was associated with IA in dominant and additive models ( OR = 0.67 , 95% CI = 0.46–0.98, P = 0.041 ; OR = 0.71 , 95% CI = 0.51–0.98, P = 0.034 , respectively). IL1A rs17561 was associated with single IA susceptibility (dominant model: OR = 0.52 , 95% CI = 0.31–0.85, P = 0.040 ). The IL12B rs3181216 polymorphism was associated with single IA susceptibility in the recessive model ( OR = 0.41 , 95% CI = 0.18–0.93, P = 0.033 ). The IL12B rs2195940 polymorphism was associated with multiple IAs susceptibility (dominant model: OR = 0.28 , 95% CI = 0.09–0.89, P = 0.031 ; additive model: OR = 0.28 , 95% CI = 0.09–0.90, P = 0.032 ). TNF-α rs1799964 was associated with multiple IAs susceptibility in the dominant model ( OR = 0.54 , 95% CI = 0.30–0.97, P = 0.040 ). No associations were found between other polymorphisms and IA susceptibility. Therefore, IL1A, IL12B, and TNF-α gene polymorphisms are associated with IA susceptibility in a Chinese population.

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Haplotype Block for Inflammatory Cytokine Gene Polymorphisms in Fabry Disease.

Blood ◽

10.1182/blood.v108.11.3834.3834 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3834-3834

Author(s):

Deborah Elstein ◽

Rachael Safyan ◽

Catharina Whybra ◽

Michael Beck ◽

Gheona Altarescu

Keyword(s):

Fabry Disease ◽

Gene Polymorphisms ◽

Inflammatory Cytokine ◽

Clinical Manifestations ◽

Cytokine Gene ◽

Tnf Α ◽

Cytokine Gene Polymorphisms ◽

Alpha Galactosidase ◽

The One ◽

End Stage

Abstract Fabry disease is an X-linked disorder associated with early-onset stroke, cardiomiopathy, and progression to end-stage renal failure. Correlations between IL-6 inflammatory cytokine gene polymorphisms and Mainz Severity Score Index (MSSI) scores have been shown. Therefore, polymorphisms of other key pro- and anti-inflammatory cytokines and correlation to clinical manifestations (MSSI scores) were attempted in order to build haplotype descriptions for Fabry disease. Genotyping for IL-10[819C/T;-592C/A]; IL-1b[+3954 C/T; -511C/T]; IL-1α[-889C/T]; and TNF-α[–308G/A] was performed in 76 patients and correlated with MSSI sub-scores and with enzyme (alpha-galactosidase A) levels. Fifty normal volunteers, age- and sex-matched, were also genotyped. Of 76 patients, 31(41%) were males and 45 (59%) were females. There was no correlation between enzyme levels and any cytokine levels. Statistically significant differences were found in prevalence of TNF-α [–308G/A] genotypes: 84%GG in patients versus 63%GG in controls (p=0.038) and for IL–1α [–889C/T] genotypes: 94%CC in patients versus 21%CC in controls (p<0.001). Statistically significant differences were found in the ratio between the two polymorphisms of IL-10 (p<0.0001), between the two polymorphisms of IL-1b (p=0.001); between IL-1α [–889C/T] and IL-1beta [3954C/T] (p=0.002); and between IL-10[–592C/T] and IL-1b [3954C/T] (p=0.041). Correlations between TNF-α [–308G/A] and both kidney and neurological MSSI sub-score (both: p=0.06) and between IL-10[-819C/T] and the MSSI neurological score (p=0.03) were noted. The relationship between inflammation and Fabry disease appears to exist on several levels. There was a multiplicity of associations among the two IL-10 polymorphisms and the two IL-1b polymorphisms and the one IL-1a polymorphism. These seem to indicate that the majority of patients have at least one C allele (but more often two C alleles) for each of the five polymorphic sites. On the other hand, the majority of patients had the GG genotype of the TNF-a[−308] polymorphism which is associated with decreased production of this pro-inflammatory cytokine. We speculate that sequence variations in regulatory DNA of genes coding for important members of the interleukin inflammatory family are associated with differential effects in Fabry disease and with increased sample size, haplotype blocks might be constructed.

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Cytokine gene polymorphism: Influence in the response of bladder superficial carcinoma to the immunotherapeutic with BCG

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.5081 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 5081-5081

Author(s):

M. V. Silva ◽

F. Calais da Silva ◽

D. Ligeiro ◽

H. Trindade

Keyword(s):

Gene Polymorphisms ◽

Nucleotide Polymorphisms ◽

Cytokine Gene ◽

Cytokine Gene Polymorphism ◽

Chi Square ◽

Single Nucleotide ◽

Exact Test ◽

Cytokine Gene Polymorphisms ◽

Ifn Γ

5081 Background: Gene polymorphisms in key immunoregulatory molecules may contribute to the heterogeneity in outcome between individuals with bladder superficial carcinome receiving the immunotherapeutic treatment with BCG. This study aims to verify and identify cytokine gene polymorphisms that could influence the immune response to BCG and antitumoural action in those patients. Methods: We studied 90 patients, after turb and BCG intravesical, there where 72 responders (80 %), 18 non-responders (20%) all patients are multiple or recurrent except T1 G3 or Cis, the median follow up is 4,5 years The cytokines single nucleotide polymorphisms (SNP’s) (IL-1a (-889T/C), IL-1β (-511C/T), IL-1β (3962T/C), IL-1R (970 C/T), IL-1Ra (11100 T/C), IL-4 (-590 C/T), IL4-Ra (+576 G/A), IL-6 (-174 G/C), IL-10 (-1082GA/-819CT/-592CA), IL-12p35 (-916C/T), TGF-β (Codon 10 C/T), TNF-a (488GA/-238GA/-308GA), TNF-β (252 G/A), IFN-γ (+874 T/A)) genotypes were assessed by PCR with Sequence Specific Primers (PCR-SSP). Genotypes and allele frequencies of responders and non-responders (with tumour recidive) to the treatment were compared and evaluated by the two-sided Fisher’s exact test or Chi square and odds ratios (OR) were calculated as an estimate of relative risk. Results: It was found a correlation of cytokine gene polymorphisms to outcome of patients for both the genotype and haplotype TNF-a 488G/-238G/-308G frequencies, which are significantly higher in patients with tumour recidive after BCG treatment (non-responders 72,2% vs responders 42% OR=3,6; 95%CI 1.15 to 11.17 p=0.033). From the other genes studied, we could depict a weak association of the IL-1R 970 T/T genotype, with a higher frequency in non-responder patients (27,8% vs 4.2% in responders, p<0.05) and with IL-10 -1082 A allele also more frequent in non-responders to BCG (75% vs 54,8%; p<0.05). Conclusions: These results suggest that host genetics of immune regulatory molecules may play a role in predicting the antitumoural response after BCG treatment of bladder cancer. Confirmation of these findings in other populations is required. No significant financial relationships to disclose.

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Cytokine Gene Polymorphisms in Saudi Patients With Atopic Dermatitis: A Case-Control Study

Biomarker Insights ◽

10.1177/1177271918777760 ◽

2018 ◽

Vol 13 ◽

pp. 117727191877776 ◽

Cited By ~ 2

Author(s):

Ghaleb Bin Huraib ◽

Fahad Al Harthi ◽

Misbahul Arfin ◽

Mohammed Al-Sugheyr ◽

Sadaf Rizvi ◽

...

Keyword(s):

Atopic Dermatitis ◽

Gene Polymorphisms ◽

Case Control Study ◽

Case Control ◽

Similar Distribution ◽

Cytokine Gene ◽

Tnf Α ◽

Number Of Genes ◽

Cytokine Gene Polymorphisms ◽

Control Study

The cause of atopic dermatitis (AD) is multifactorial and a number of genes including cytokines have been involved. We genotyped 315 subjects for polymorphisms in TNF-α and TNF-β and IL-10 genes. Patients had significantly higher frequency of GA genotype of TNF-α (−308 G/A) than healthy controls. Patients with AD and controls had similar distribution of A and G alleles. Genotype AA was found in 7.11% of controls while completely absent in cases. The frequencies of genotypes GG and AA of TNF-β (+252 A/G) polymorphism were higher whereas the frequency of genotype GA was significantly lower in patients than the controls. The frequencies of genotypes GG and AA of IL-10 (1082 G/A) polymorphism were significantly increased whereas genotype GA was decreased in patients than the controls. It is concluded that TNF-α (−308 G/A), TNF-β (+252 A/G), and IL-10 (−1082 G/A) polymorphisms are linked with the susceptibility of AD in Saudis and can be a risk factor.

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Cytokine Gene Polymorphisms in Cancer and Inflammatory Disorders

Current Immunology Reviews ◽

10.2174/1573395514666180724121419 ◽

2018 ◽

Vol 14 (2) ◽

pp. 81-93

Author(s):

Hanim Kamis Norhalifah ◽

Nor Fazila Che Mat ◽

Hisham Atan Edinur

Keyword(s):

Gene Polymorphisms ◽

Cytokine Gene ◽

Inflammatory Disorders ◽

Cytokine Gene Polymorphisms

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FRI0550 CAN CYTOKINE GENE POLYMORPHISMS BE USEFUL FOR THE THERAPEUTIC CHOICE IN JAPANESE PATIENTS WITH RHEUMATOID ARTHRITIS?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2067 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 876.2-877

Author(s):

S. Tsujimoto ◽

M. Shigesaka ◽

A. Tanaka ◽

Y. Ozaki ◽

T. Ito ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Autoimmune Disease ◽

Gene Polymorphisms ◽

Therapeutic Response ◽

Bone Erosion ◽

Japanese Patients ◽

Cartilage Degradation ◽

Cytokine Gene ◽

Biological Dmards ◽

Cytokine Gene Polymorphisms

Background:Rheumatoid arthritis (RA) is a common autoimmune disease. It is characterized by systemic synovitis with bone erosion and joint cartilage degradation(1). Production of autoantibody is important for autoimmune disease. Cytokines play crucial roles in its pathogenesis(2). SNP distribution varies between races. Few studies have examined SNP targeted at Japanese patients. The analysis of cytokine gene polymorphisms is important factor of pathophysiology and treatment.Objectives:This analysis was aimed to investigate the association between cytokine gene polymorphisms and autoantibody and therapeutic response in Japanese RA patients.Methods:This study subjects consisted of 100 RA patients and 50 healthy controls. We extracted data on patient sex, age, disease duration, rheumatoid factor (RF), anti cyclic citrullinated peptide (anti-CCP) antibody and therapeutic response including methotrexate (MTX) and biological DMARDs. Genomic DNA was isolated from peripheral blood, these were genotyped for TNFα, TGFβ1, IL-6, IL-10 and IFNγ polymorphisms. We analyzed these data using a chi-square test.Results:IL-10 (-819 C/T and -592 C/A) revealed that there were significant decrease in the frequency of IL-10 (-819) CC genotype and (-592) CC genotype as compared to controls in RA patients. Genotyping of IL-10 showed that there was significant decrease ACC/ACC genotype (Table 1).IFNγ (+874 A/T) revealed that there was significant decrease in the frequency of TT genotype as compared to controls (Table 1).No significant differences in TNFα, TGFβ1and IL-6 genotypes and alleles frequency were observed between RA patients and control.TGFβ1(+869 A/T) in patients with anti-CCP antibody positive revealed that there was significant decrease in the frequency of TT genotype as compared to patients with anti-CCP antibody negative (Table 2).No significant association between RF and any cytokine gene polymorphism.Analyzing cytokine gene polymorphisms could be useful for treatment with MTX and biological DMARDs.Table 1.Table 2.Conclusion:IL-10 (-819 C/T, -592 C/A) and IFNγ (+874 A/T) polymorphism might be related to RA in Japanese population. In addition, TGFβ1(+869 A/T) polymorphism might be associated with the production of anti-CCP antibody. These results suggest that the analyzing cytokine gene polymorphisms may offer promise as useful factors in the choice of treatment for Japanese RA patients.References:[1] Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet. 2010; 376: 1094–108.[2] McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007 Jun;7(6):429-42.Disclosure of Interests:None declared

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