Cytokine gene polymorphism as a factor of predisposition to development of chronic purulent otitis media

2019 ◽  
pp. 4-14
Author(s):  
Е.В. Байке ◽  
О.И. Уразова
Keyword(s):  
Otitis Media ◽  
Odds Ratio ◽  
Gene Polymorphisms ◽  
Cytokine Gene ◽  
Cytokine Gene Polymorphism ◽  
Homozygous Genotype ◽  
Tnf Α ◽  
Il10 Gene ◽  
Polymorphic Variants ◽  
Il1b Gene

В последние десятилетия распространенность хронического гнойного среднего отита (ХГСО) заметно выросла. Значительная роль при воспалении, в том числе в патогенезе ХГСО, отводится клеточным медиаторам - цитокинам. Доказана роль полиморфизма генов цитокинов в развитии заболеваний, ассоциированных с воспалительными процессами. Цель работы - проанализировать взаимосвязь полиморфизма генов IL1В (С3953Т, С511Т, Т31С), IL10 (G1082A, C592A, C819T), IL6 (С174G) и TNFА (G308A) с развитием ХГСО и возрастным фактором начальных его проявлений. Методика. Распределение генотипов аллельных вариантов генов цитокинов (IL-1, IL-6, IL-10 и TNF-α) анализировали у 299 пациентов с ХГСО в зависимости от сроков начала заболевания (в возрасте до 14 лет, от 15 до 30 лет, старше 30 лет). Контрольную группу составили 183 здоровых добровольца с сопоставимым распределением по полу и возрасту. Для определения полиморфных вариантов генов IL1В (-3953, -511, -31), IL10 (-1082, -592, -819), IL6 (-174) и TNFА (-308) применяли метод ПЦР в режиме реального времени. Об ассоциации генотипов с заболеванием судили по величине отношения шансов (Odds Ratio (OR)) и коэффициентов Юла (Q) и контингенции (Фи, Φ). За критический уровень значимости при проверке статистических гипотез принимался p≤0,05. Результаты. Выявлено, что к развитию ХГСО предрасполагают полиморфные варианты генов цитокинов IL1В, IL10 и TNFА. Наиболее значимыми в формировании предрасположенности к развитию заболевания являются генотипы С/С полиморфизмов С3953Т и Т31С гена IL1В, А/А полиморфизма G1082A и Т/Т полиморфизма С819Т гена IL10. Полиморфные варианты генов IL1В (генотип C/C полиморфизмов С3953Т и Т511С) и IL10 (генотип А/A полиморфизма G1082A) сочетаются с дебютом ХГСО в возрасте до 14 лет. Полиморфизм C174G гена IL6 не оказывает предрасполагающего влияния на развитие болезни. Протективный эффект в отношении развития ХГСО связан с носительством гомозиготного генотипа Т/Т полиморфизмов С511Т и Т31С гена IL1В и гомозиготного генотипа G/G полиморфизма G1082A гена IL10. Заключение. К развитию ХГСО предрасполагают полиморфизмы генов про- и противовоспалительных цитокинов, дисбаланс которых обусловливает патологическое течение иммунного ответа и раннюю (в детском возрасте) клиническую манифестацию болезни. In recent decades, prevalence of chronic purulent otitis media has increased markedly. A significant role in inflammation, including the pathogenesis of chronic purulent otitis media, is assigned to the cellular mediators, cytokines. The predisposing role of cytokine gene polymorphism in development of inflammatory-associated diseases has been proven. Aim. To analyze the relationship of IL1B (C3953T, C511T, T31C), IL10 (G1082A, C592A, C819T), IL6 (C174G), and TNFA (G308A) gene polymorphisms with development of chronic purulent otitis media and the age of its primary manifestation. Methods. Distribution of genotypes of allelic variants in cytokine (IL-1, IL-6, IL-10 and TNF-α) genes was analyzed in 299 patients (129 men and 170 women aged 38.0 ± 4.3) based on the age of disease onset (with chronic purulent otitis media diagnosed at age of 14, from 15 to 30, and older than 30). The control group consisted of 183 sex- and age matched healthy volunteers. Genomic DNA was isolated from whole blood leukocytes. Real-time PCR was used for determination of polymorphic variants in IL1B (-3953, -511, -31), IL10 (-1082, -592, -819), IL6 (-174), and TNFA (-308) genes. The association of genotypes with the disease was evaluated by the odds ratio (OR) and the values of Yule (Q) and contingent (Phi, Φ) coefficients. The critical significance level for the statistical hypotheses tests was taken as <0.05. Results. IL1B, IL10, and TNFA cytokine gene polymorphisms predisposed to development of chronic purulent otitis media. The genotypes C/C of C3953T and T31C polymorphisms in the IL1B gene, A/A of G1082A polymorphism, and T/T of C819T polymorphism in the IL10 gene are the most significant ones in the predisposition to disease development. Polymorphic variants of IL1B (C/C genotype of C3953T and T511C polymorphisms) and IL10 (A/A genotype of G1082A polymorphism) genes are associated with the onset of chronic purulent otitis media at age of 14. The C174G polymorphism in the IL6 gene does not predispose to the disease. Protection from the development of chronic purulent otitis media is associated with carriage of the T/T homozygous genotype of C511T and T31C polymorphisms in the IL1B gene and the G/G homozygous genotype of G1082A polymorphism in the IL10 gene. Conclusion. Polymorphisms of pro- and anti-inflammatory cytokine genes predispose to the development of chronic purulent otitis media. An imbalance of these cytokines results in a pathological course of immune response and early (children) clinical manifestation of the disease.

Association of cytokine gene polymorphisms and risk factors with otitis media proneness in children

2016 ◽  
Vol 175 (6) ◽  
pp. 809-815 ◽  
Author(s):  
Olivera Miljanović ◽  
Bojana Cikota-Aleksić ◽  
Dragan Likić ◽  
Danilo Vojvodić ◽  
Ognjen Jovićević ◽  
...  
Keyword(s):  
Risk Factors ◽  
Otitis Media ◽  
Gene Polymorphisms ◽  
Cytokine Gene ◽  
Cytokine Gene Polymorphisms

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

2019 ◽  
Vol 21 (5) ◽  
pp. 552-563
Author(s):  
Sahereh Mirzaei ◽  
Larisa Burke ◽  
Anne G. Rosenfeld ◽  
Susan Dunn ◽  
Jennifer R. Dungan ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Gene Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Cytokine Gene ◽  
Chest Discomfort ◽  
Specific Symptom ◽  
Arm Pain ◽  
Coronary Syndrome ◽  
Tnf Α ◽  
Cytokine Gene Polymorphisms

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.

Profile of cytokine gene polymorphisms in Iranian multiple sclerosis patients

2007 ◽  
Vol 13 (2) ◽  
pp. 253-255 ◽  
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

Cytokine gene polymorphism in kidney transplantation — Impact of TGF-β1, TNF-α and IL-6 on graft outcome

2008 ◽  
Vol 18 (4) ◽  
pp. 344-348 ◽  
Author(s):  
Penka N. Nikolova ◽  
Milena I. Ivanova ◽  
Snejina M. Mihailova ◽  
Anastassia P. Myhailova ◽  
Daniela N. Baltadjieva ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Gene Polymorphism ◽  
Cytokine Gene ◽  
Cytokine Gene Polymorphism ◽  
Graft Outcome ◽  
Tnf Α ◽  
Tgf Β1

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

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.

scholarly journals TNF-α and IL-1 β Cytokine Gene Polymorphism in Patients with Nasal Polyposis

2017 ◽  
Vol 55 (2) ◽  
pp. 51-56 ◽  
Author(s):  
Onur Ismi ◽  
Cengiz Ozcan ◽  
Gurbuz Polat ◽  
Seval Kul ◽  
Kemal Gorur ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Nasal Polyposis ◽  
Cytokine Gene ◽  
Cytokine Gene Polymorphism ◽  
Tnf Α

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

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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