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

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.

Association of IL-10 (− 1082 A/G) and IL-6 (− 174 G/C) gene polymorphism with type 2 diabetes mellitus in Ethiopia population

Background Interleukin (IL)-6 and IL-10 are the most important cytokine with pro and anti-inflammatory activities, respectively. Dysregulation of IL-6 and IL-10 are associated with increased risk of developing Type 2 Diabetes Mellitus (T2DM). Despite this, a fundamental understanding of both cytokine gene polymorphisms with its expression is critical in understanding of cellular mechanism of insulin resistance as well as T2DM intervention. Therefore, this study aimed to assess IL-6 (− 174 G/C) and IL-10 (− 1082 A/G) gene polymorphism, and its association with T2DM, North West Ethiopia. Methods A comparative cross-sectional study from January to May 2018 was conducted on study participants with T2DM and apparently healthy controls. Deoxyribonucleic acid (DNA) extraction and genotyping was carried out by using amplification refractory mutation system polymerase chain reaction to detect polymorphism of IL-6 and IL-10 gene at the position − 174 and − 1082, respectively. The logistic regression model was fitted to assess the association of between cytokine gene polymorphisms and T2DM. Odds ratio with 95% CI was determined to assess the presence and strength of association between the explanatory variables and outcome variable. A P-value < 0.05 was considered as statistically significant. Result Participants carrying the GG genotype of IL-6 (− 174) (OR (95% CI) = 4.61 (2.07–10.54) was a high likelihood of having T2DM compared to those carrying the CC and AA genotypes. AA and AG genotypes of IL-10 (− 1082) were at lower odd of developing T2DM compared to those carrying the GG genotype. In addition, individuals carrying the G allele of IL-6 (− 174) have 2.82-fold odds of developing T2DM compared to individuals carrying the C allele (OR (95% CI) =2.81 (1.78–4.50)). Conclusion Our study revealed that genetic polymorphisms of IL-6 (− 174) GG genotype is the potential host genetic risk factors to T2DM. While, IL-10 (− 1082) AA genotype is negatively associated with T2DM. Therefore, IL-6 (− 174) and IL-10 (− 1082) genetic variation may be considered as a biomarker for early screening and diagnosis of T2DM.

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

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.