IL-8 Rs4073 Polymorphisms Research Articles

Polymorphism of Genes Encoding Inflammatory Interleukins and the Risk of Anterior Cruciate Ligament Injury: A Systematic Review and Meta-Analysis.

Sport injuries, including the anterior crucial ligament rupture (ACLR) seem to be related to complex genetic backgrounds, including the genes responsible for inflammatory response. This review and meta-analysis investigated the contribution of the polymorphisms of genes encoding inflammatory cytokines and their receptors to the risk of ACLR. The scientific databases Science Direct, EBSCO host, Scopus, PubMed, and Google Scholar were screened (completed on 14 June 2023) according to the established inclusion/exclusion criteria (only fully accessible, original, human case-control studies written in English concerning the effect of interleukin genes' polymorphisms on the occurrence of ACL injury were included) and statistical meta-analysis using R version 4.0.3 was performed. The PRISMA methodology was used to review articles. The review protocol was registered under the number CRD42024514316 in the Prospero database. Eighty-nine studies were identified and narrowed down to three original case-control studies used for the meta-analysis. The studies analyzed Polish, South African, and Swedish cohorts, altogether 1282 participants. The candidate polymorphisms indicated in the studies involved IL6 rs1800795, IL6R rs2228145 and IL1B rs16944. The systematic review showed the relationships between IL6 rs1800795 polymorphism and ACLR in the Polish subpopulation, and IL6R rs2228145 and IL1B rs16944 in the South African subpopulations. The meta-analysis revealed that the IL6 rs1800795 CG genotype was over-represented (OR = 1.30, 95% CI 1.02-1.66), while the CC genotype was under-represented (OR = 0.75, 95% CI 0.54-1.03) in ACLR subjects, but no significant impact of IL6R rs2228145 was shown. Additionally, a tendency of the IL1B rs16944 CT genotype to be protective (OR 0.89, 95% CI 0.70-1.14), while the TT to be a risk genotype (OR 1.19, 95% CI 0.84-1.68) was observed. Thus, the relationship between the interleukin receptor IL6R rs2228145 and ACLR risk was not confirmed. However, the impact of genes coding pleiotropic IL6 rs1800795 on the incidences of ACLR was clear and the effect of pro-inflammatory IL1B rs16944 was possible.

Immune gene polymorphisms associated with poor response to platelet transfusion and recombinant factor VII administration in Glanzmann thrombasthenia.

Poor response to platelet and recombinant factor VII administration is a major problem in patients with Glanzmann Thrombasthenia (GT). The risk factors associated with poor response to treatment in these patients are unknown. Some genetic variations of cytokines may contribute to therapy resistance. We evaluated, for the first time, whether genetic polymorphisms on cytokine genes are related to poor treatment response in GT patients. We enrolled 30 patients with GT (15 resistant and 15 non-resistant) and 100 healthy controls. Gene polymorphisms of IL-10 and TNF-α were analysed using TaqMan Realtime PCR, and IL-1, IL-1R1 and IL-1RN were investigated with the RFLP method. In-silico analyses were performed to predict the potential impact of these polymorphisms. In the resistant group, all patients had a variant of the IL-10 gene at the -1082 position (rs1800896), with a GG genotype that was significantly more frequent than the non-resistant group. Analysis between healthy controls and GT patients revealed a probable correlation between rs3783550, rs3783553, rs3917356 and rs2234463 and GT. The In-silico study indicated that TNF-α rs1800629 and IL-10 rs1800896 polymorphisms result in different allelic expressions which may contribute to poor response to therapy. These findings suggest that polymorphisms in the IL-10 and IL-1 receptor antagonist genes may play a role in poor therapy response in GT patients. In addition, some polymorphisms in IL-1α, IL1-β, IL-1R1 and IL-R antagonists might be involved in the GT progression.

Association of IL-4 (− 590 C/T) and IL-6 (− 174 G/C) gene polymorphism in South Indian CKD patients

AimThe present study was undertaken to examine the role of IL-4 (− 590 C/T) (rs2243250) and IL-6 (− 174G/C) (rs1800795) polymorphism and the serum levels of IL-4 and IL-6 in chronic kidney disease (CKD).MethodsThe IL-4 (− 590C/T) and IL-6 (− 174 G/C) polymorphisms were genotyped in 132 CKD patients and 161 controls using PCR–RFLP. Serum IL-4 and IL-6 quantifications were performed by ELISA.ResultsSignificant susceptible associations of CT genotype (OR = 4.56; p < 1.84 × 10–9) and T allele (OR = 1.56; p < 0.010) of IL-4 (− 590C/T) and CC genotype (OR = 2.63; p < 0.032) of IL-6 (− 174G/C) were observed for CKD. The CC genotype (OR = 0.27; p < 9.314 × 10–7) and C allele (OR = 0.63; p < 0.010) of IL-4 (− 590 C/T) revealed strong protective associations. Five-fold increased levels were observed for both IL-6 (p < 0.0001) and IL-4 (p < 0.0043) cytokines in CKD patients than the controls. The IL-4 serum levels (pg/ml) increased significantly in patients with CT and TT genotypes of IL-4 (− 590 C/T) than the controls (6.18 ± 1.80 vs. 3.33 ± 0.48 and 6.14 ± 1.96 vs. 3.21 ± 0.56 respectively). For IL-6 (− 174 G/C) polymorphism, the patients with CC genotype (6.50 ± 1.30 vs. 3.49 ± 1.39) revealed with higher IL-6 serum levels followed by GC genotype (5.00 ± 1.91 vs. 4.01 ± 1.74).ConclusionThe genotypes of IL-4 (590 C/T) and IL-6 (174 G/C) polymorphisms contribute differential susceptibility in south Indian CKD patients. A fivefold increased serum levels of IL-4 (anti-inflammatory) and IL-6 (pro- and anti-inflammatory) cytokines were documented in CKD patients. There observed an opposite trend in disease association for these two cytokines and associated SNPs with CKD in south India.

Role of the IL8 rs4073 polymorphism in central nervous system toxicity in patients receiving multidrug-resistant tuberculosis treatment.

To determine the role of the IL8 rs4073 polymorphism in predicting the risk of central nervous system (CNS) toxicity in patients receiving standard pharmacological treatment for multidrug-resistant tuberculosis (MDR-TB). A cohort of 85 consenting MDR-TB patients receiving treatment with second-line antituberculosis drugs had their blood samples amplified for the IL8 (rs4073) gene and genotyped. All patients were clinically screened for evidence of treatment toxicity and categorized accordingly. Crude and adjusted associations were assessed. The chief complaints fell into the following categories: CNS toxicity; gastrointestinal toxicity; skin toxicity; and eye and ear toxicities. Symptoms of gastrointestinal toxicity were reported by 59% of the patients, and symptoms of CNS toxicity were reported by 42.7%. With regard to the genotypes of IL8 (rs4073), the following were identified: AA, in 64 of the study participants; AT, in 7; and TT, in 11. A significant association was found between the dominant model of inheritance and CNS toxicity for the crude model (p = 0.024; OR = 3.57; 95% CI, 1.18-10.76) and the adjusted model (p = 0.031; OR = 3.92; 95% CI, 1.13-13.58). The AT+TT genotype of IL8 (rs4073) showed a 3.92 times increased risk of CNS toxicity when compared with the AA genotype. The AT+TT genotype has a tendency to be associated with an increased risk of adverse clinical features during MDR-TB treatment.

Characterisation ofIGF-1 (rs7136446) and IL-6 (rs1800795) polymorphisms among breast cancer patients in western Algeria.

Breast cancer (BC) is themost frequently diagnosed cancer among women worldwide, including Algeria. Certain single nucleotide polymorphisms (SNPs) have been linked to higher risk ofBC. Several studies have been performed on theinsulin- like growth factor 1 (IGF-1) T > C (rs7136446) and theinterleukin 6 (IL-6) 174 G > C (rs1800795) SNPs to explore their role in BC. Theaim ofthis study is to investigate theassociation between the2 SNPs, IL-6 (rs1800795) and IGF-1 (rs7136446) with BC in thepopulation ofwestern Algeria. This study was carried out for thefirst time among theAlgerian population. This case-control study included 109 BC patients and 112 healthy controls. Genomic DNA was extracted from peripheral blood samples. DNA concentration was determined using theQubit 2.0 fluorometer. Thegenotyping ofselected SNPs was performed by real-time polymerase chain reaction followed by statistical analysis to assess genotypic frequencies and genetic association with BC. Theresults showed that IGF-1 rs7136446 was positively associated with BC (p = 0.00001) and that thedistribution ofgenotype frequencies ofrs7136446 showed astatistically difference between human epidermal growth factor receptor 2 (HER-2) positive and HER-2 negative BC (p = 0.04), but this association did not last after thecorrection ofBonferroni. No association was found in genotype distribution oftheIL-6 (rs1800795) among controls and BC patients or with clinicopathological parameters including HER-2 status in BC (p > 0.05). In summary, our findings indicate that IGF-1 rs7136446 is associated with BC in our population ofwestern Algeria.

Interleukins-6 −174G/C (rs1800795) and −572C/G (rs1800796) polymorphisms and prostate cancer risk

Prostate cancer (PCa) is an aggressive cancer influenced by a complex interplay of genetic and environmental factors. Amongst these risk factors, the impact of Interleukin6 (IL6) gene polymorphisms in PCa risk has received a lot of attention. IL-6 is a cytokine that has been implicated in the pathogenesis of several malignancies, including PCa. Two IL-6 gene polymorphisms, − 174 G/C (rs1800795) and − 572 C/G (rs1800796), have received intellectual attention due to their potential role as modulators of prostate cancer risk. The main objective of this research was to comprehensively explore the potential associations between IL-6 rs1800795 and rs1800796 polymorphisms, and their impact on the occurrence of PCa. A case-control study was carried out with a well-defined cohort comprising 110 PCa cases and 110 controls (total n = 220). The genotyping of rs1800795 and rs1800796 was carefully performed using the highly sensitive and accurate Polymerase Chain Reaction-High Resolution Melting Curve (PCR-HRM) technique. The assessment of genetic associations was evaluated using various R packages, such as Haplo-Stats, SNP stat, pheatmap, and LD heatmap. The present study applied odds ratio (OR) analysis to reveal significant evidence of strong associations between the genotypes of rs1800795 and rs1800796 and the susceptibility to PCa. The findings of this study underscore the noteworthy impact of genetic variations in the IL-6 gene on the development of prostate cancer. Specifically, the C/G and G/G genotypes of rs1800795 demonstrated increased PCa risk, with odds ratios (OR) of 1.650 (95% CI = 1.068–2.549, p = 0.032) and 2.475 (95% CI = 1.215–5.043, p < 0.001), respectively. Similarly, the G/C genotype of rs1800796 exhibited an OR of 2.374 (95% CI = 1.363–4.130, p = 0.012) for elevated prostate cancer risk, while the C/C genotype had an OR of 1.81 (95% CI = 1.02–3.22, p = 0.7). Furthermore, our haplotype analysis have revealed an association between haplotype 4 (C-G) and increased risk of PCa (OR = 1.69, 95% CI = 1.05–2.73, p = 0.032). In conclusion, this case-control analysis presents compelling evidence for a significant association between IL-6 variants (rs1800795 and rs1800796) and increased susceptibility to prostate cancer.

PPARA and IL6: exploring associations with athletic performance and genotype polymorphism.

This study aims to investigate the Interleukin (IL)-6 rs1800795 and peroxisome proliferator-activated receptor alpha (PPARA) rs4253778 polymorphism distributions in the relatively faster and slower subgroups of national cross-country skiing athletes and to identify advantageous genotypes for endurance performance. IL-6 is an inflammatory mediator that is effective in muscle tissue hypertrophy, repair, and the immune system. On the other hand, PPARA transcription factor is a molecule associated with fatty acid, sugar metabolism and inflammation formation. Total of 30 professional cross-country skiing athletes were examined in three groups as athletes, female athletes, and male athletes. DNA of the participants were isolated from blood and genetic polymorphisms were determined by RT-PCR. Athletes were divided into two subgroups as faster and slower referring to their "1-kilometer cross-country skiing time averages (CCSTA)". Polymorphism distributions in these subgroups were analyzed statistically with Fisher's exact test and descriptive tests. In addition, the 1 km-CCSTA values of the genotypes were determined by descriptive statistical methods and the time advantages were calculated. It was determined that the combination of IL-6 rs1800795 GC and PPARA rs4253778 GG genotypes was observed to be more prominent among the faster categories of cross-country skiing competitors, particularly in the athletes and male athletes categories, and it had a time advantage at 1 km-CCSTA. The GC genotype (p= 0.0098) and C-allele (p=0.0398) of IL-6 rs1800795 polymorphism were detected at a higher rate in the fast subgroup in male athletes. These genotypes may support endurance performance.

Association between IL10 rs1800896 polymorphism and risk of pediatric asthma: A meta-analysis.

Asthma is a common chronic condition in children. Several studies have explored the potential association between IL10 rs1800896 polymorphism and the risk of asthma in children, but the findings have been inconsistent. To address these discrepancies, we conducted a systematic review and meta-analysis to assess the relationship between IL10 rs1800896 polymorphisms and the susceptibility to pediatric asthma. A literature search was conducted in PubMed, Scopus, Web of Science, and CNKI databases to identify eligible studies through April 2022. Meta-analysis was then performed using five genetic models: dominant, recessive, homozygous, heterozygous, and allele. A total of 12 studies comprising 1645 cases along with 1447 controls were included in this meta-analysis. It was found that rs1800896 was not associated significantly with susceptibility to childhood asthma in all genetic models investigated. Subgroup analysis based on the ethnic background of the subjects revealed that rs1800896 was significantly linked to a lower risk of pediatric asthma among Asians in the homozygous model (OR = 0.311, 95% CI = 0.152-0.637, P = 0.001) and in the recessive model (OR = 0.585, 95% CI = 0.405-0.846, P = 0.004), whereas no significant relationship was observed in Egyptians (P > 0.05). In conclusion, IL10 rs1800896 polymorphism may be useful as a predictive marker for childhood asthma in Asians, although further studies are needed to validate the study results.

The association of cytokines genes (IL-6 and IL-10) with the susceptibility to schizophrenia: A systematic review and meta-analysis

Cytokines are among the important effectors and messenger molecules for restoring the homeostasis tissue after an inflammatory response. The association between IL-6 and IL-10 genes polymorphisms with the schizophrenia susceptibility have yielded controversial results. To reconcile the results, a systematic review followed by meta-analysis was performed to assess the association. We carried out literature searches of PubMed, Scopus, EBSCO, and Web of Sciences databases. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Subgroup analysis, heterogeneity analyses, and publication bias were also calculated in the meta-analysis. A total of 22 case-control studies, consisting of 4,993 schizophrenic patients and 5,195 healthy controls, were included in the meta-analysis. The meta-analysis suggests that the IL-6 rs1800795 polymorphism displays a protective role against schizophrenia, while the IL-10 rs1800896 and rs1800872 polymorphisms confer an increased risk of schizophrenia. Similar results were found in subgroup analysis by ethnicity. We did not find association between IL-10 rs1800871 polymorphism and schizophrenia susceptibility. Finally, this meta-analysis suggested that the dysregulation of cytokines could lead to the pathogenesis of the schizophrenia.

Association of interleukin-10 rs1800896, rs1800872, and interleukin-6 rs1800795 polymorphisms with squamous cell carcinoma risk: A meta-analysis.

The relationship between interleukin (IL)-10 and IL-6 gene polymorphisms and squamous cell carcinoma (SCC) has been demonstrated but with inconsistent conclusions. The aim of this study was to evaluate the potential associations of IL gene polymorphisms and the SCC risk. PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biomedical Database, WanFang, and China Science and Technology Journal Database databases were searched for articles reporting the correlations of IL-10 and IL-6 gene polymorphisms with the SCC risk. Odds ratio and 95% confidence interval were calculated using Stata Version 11.2. Meta-regression, sensitivity, and publication bias were analyzed. False-positive reporting probability and Bayesian measure of the false-discovery probability were used to explore the credibility of the calculation. Twenty-three articles were included. The IL-10 rs1800872 polymorphism showed a significant correlation with the SCC risk in the overall analysis. Studies pooled by ethnicity revealed that the IL-10 rs1800872 polymorphism reduced the SCC risk in the Caucasian population. The results of this study suggest that the IL-10 rs1800872 polymorphism may confer a genetic susceptibility to SCC, particularly oral SCC, in Caucasians. However, the IL-10 rs1800896 or IL-6 rs1800795 polymorphism was not significantly associated with the SCC risk.

Influence of IL-6 rs1800795 and IL-8 rs2227306 polymorphisms on COVID-19 outcome.

Severe coronavirus disease 2019 (COVID-19) is mainly precipitated by an uncontrolled inflammatory response and cytokine storm. Pro-inflammatory cytokines such as IL-6 and IL-8 levels were markedly increased in complicated cases. Genetic polymorphisms may have a role in this dysregulated expression during SARS-CoV-2 infection. Our aim was to assess the influence of IL-6 and IL-8 single nucleotide polymorphisms (SNPs) on COVID-19 outcomes. 240 subjects were involved in the study; 80 cases with severe COVID-19, 80 cases with mild COVID-19, and 80 healthy subjects. IL-6rs1800795(G/C) and IL-8 rs2227306(C/T) genotyping was performed using real-time polymerase chain reaction (PCR). Ages ranged between 20-67 years in all groups. There was a statistically significant association between the male gender and severe COVID-19. A significantly higher expression of IL-6rs1800795GG and IL-8rs2227306CC genotypes was observed among patients with severe COVID-19 than other groups. At the allele level, IL-6rs1800795G and IL-8rs2227306C alleles were more frequent among patients with severe COVID-19 when compared with other groups. Haplotypes' frequency clarified that the coexistence of IL-6 rs1800795G and IL-8rs2227306C alleles in the same person increased the risk of severe COVID-19 outcomes. Carriers of IL-6rs1800795C and IL-8 rs2227306T alleles are at lower risk of developing severe COVID-19. Multivariate logistic regression analysis showed that old age, male gender, IL-6 rs1800795CG+GG, and IL-8 rs2227306CT+CC genotypes could be independent risk factors for severe COVID-19 outcomes. IL-6 rs1800795G and IL-8 rs2227306C alleles are significantly associated with severe COVID-19 outcomes, especially if they coexist. They may be used as prognostic markers for COVID-19.

Investigation of association between IL-6 level, il6 and il6r variants and community acquired pneumonia among Iranian children

BackgroundCommunity-acquired pneumonia (CAP) is known as a dangerous illness accounted for approximately 20% of mortality in children younger than five years around the world. Regarding the immaturity of the immune system in this group; they are more inclined to infections particularly, CAP. In the onset of pneumonia, pro-inflammatory cytokines such as interleukin (IL)-1, tumor necrosis factor-α and IL-6 are essential for amplifying local immune response against the pathogen(s). As IL-6 is a multipotent cytokine with dual pro- and anti-inflammatory functions, this study aimed to evaluate the association of IL-6 level and the variants in IL-6 and IL-6 receptor (R) genes with community-acquired pneumonia in children under five years. Materials and methodsThis case–control study included 126 children with CAP and 70 healthy control children who matched the case group by age and sex. IL-6 rs1800795 and IL-6R rs8192284 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP); also, the serum IL-6 levels were measured by enzyme-linked immunosorbent assay (ELISA) method. ResultsCompared to the healthy controls, the frequency of AC genotypes and allele A in IL6R rs8192284 were significantly higher in the CAP group compared with those in the controls (P value = 0.01 and 0.00001, respectively). Although the serum level of IL-6 was not significantly different between two groups, higher IL-6 level was associated with febrile condition (P = 0.001). ConclusionThe results revealed that carriage of A allele and AC genotype at rs8192284 position of IL-6R may be a predisposing factor for CAP in children and increased level of IL-6 is associated with the presence of clinical manifestation such as fever. So, this factor could be added to the inflammatory panel for assessing the severity of disease as well as lung injury in children with CAP.

IL6 gene polymorphism association with calcific aortic valve stenosis and influence on serum levels of interleukin-6.

Aortic valve stenosis is the most frequent valve disease in developed countries and its prevalence will increase with population aging. There is still no pharmaceutical treatment nor biomarker to determine the susceptibility to develop aortic stenosis. Therefore, we analyzed the association of polymorphisms in risk loci with calcific aortic stenosis. Patients with aortic valve disease were genotyped for PALMD rs6702619, LPA rs10455872, and IL6 rs1800795 polymorphisms and circulating levels of interleukin-6 (IL-6) were measured. Calcium content of leaflets obtained in valve replacement surgeries was determined by micro-computed tomography. In the genotyping of 578 individuals, we found significant association between PALMD and IL6 polymorphisms and aortic stenosis in patients with tricuspid aortic valve, independently of other potentially confounding variables such as age and dyslipidemia. There was no association of these polymorphisms with valve calcium content, but this value correlated with the mean aortic pressure gradient (r = 0.44; P < 0.001). The CC genotype of IL6 polymorphism was associated with higher levels of serum IL-6 compared to other genotypes (23.5 vs. 10.5 pg/ml, respectively; P = 0.029). Therefore, patients carrying the CC genotype of IL6 rs1800795 polymorphism present higher levels of circulating IL-6 and this could contribute to the severity of the aortic valve stenosis. Our results agree with the identification of IL6 as a locus risk for stenosis and also with the intervention of this cytokine in aortic valve calcification. A more exhaustive follow-up of those patients carrying risk genotypes is therefore recommended.

Development of a genetic risk score for obesity predisposition evaluation.

Obesity is a major public health issue resulting from an interaction between genetic and environmental factors. Genetic risk scores (GRSs) are useful to summarize the effects of many genetic variants on obesity risk. In this study, we aimed to assess the association of previously well-studied genetic variants with obesity and develop a genetic risk score to anticipate the risk of obesity development in the Iranian population. Among 968 participants, 599 (61.88%) were obese, and 369 (38.12%) were considered control samples. After genotyping, an initial screening of 16 variants associated with body mass index (BMI) was performed utilizing a general linear model (p < 0.25), and seven genetic variants were selected. The association of these variants with obesity was examined using a multivariate logistic regression model (p < 0.05), and finally, five variants were found to be significantly associated with obesity. Two gene score models (weighted and unweighted), including these five loci, were constructed. To compare the discriminative power of the models, the area under the curve was calculated using tenfold internal cross-validation. Among the studied variants, ADRB3 rs4994, FTO rs9939609, ADRB2 rs1042714, IL6 rs1800795, and MTHFR rs1801133 polymorphisms were significantly associated with obesity in the Iranian population. Both of the constructed models were significantly associated with BMI (p < 0.05) and the area under the mean curve of the weighted GRS and unweighted GRS were 70.22% ± 0.05 and 70.19% ± 0.05, respectively. Both GRSs proved to predict obesity and could potentially be utilized as genetic tools to assess the obesity predisposition in the Iranian population. Also, among the studied variants, ADRB3 rs4994 and FTO rs9939609 polymorphisms have the highest impacts on the risk of obesity.

The Relationship between Swimming Styles and Il-6 Rs1800795 Polymorphism in Professional Swimmers

Background: Athletic performance can be improved with regular training, the contribution of genetic factors, nutrition and psychological factors. The aim of this study is to determine the effect of IL-6 rs1800795 polymorphism in Turkish swimmers and to compare the results with sedentary individuals. Material and Methods: 75 people, including 45 professional swimmers and 30 healthy and sedentary individuals (control), participated in the study. DNA isolation from buccal specimens of athletes was performed using the commercial kit Invitrogen (Van Allen Way, Carlsbad, CA, USA). Genotyping was performed with real-time PCR. Results: GG genotype and G allele were found to be higher in athletes. GG genotype and G allele were found to be higher in the control group. There was no statistically significant difference between the athletes and controls in terms of IL-6 rs1800795 polymorphism. In our study, when the IL-6 rs1800795 gene polymorphism was compared between the groups in terms of swimming styles-distances and genotypes, no significant difference was found. Conclusion: Our study is the first to analyze the IL-6 rs1800795 polymorphism in Turkish swimmers. More studies are needed in terms of IL-6 rs1800795 to reveal the importance of genetic factors in determining the sports performance of the athlete and to clarify their effects on athletic performance. This first report, which includes relevant genetic markers and swimmers, will guide scientists for further studies. Keywords: Genetics, Polymorphisms, Sports Genetics, Single Nucleotide Polymorphism, Swimmers, IL-6

A Meta-Analysis for Association of XRCC3 rs861539, MTHFR rs1801133, IL-6 rs1800795, IL-12B rs3212227, TNF-α rs1800629, and TLR9 rs352140 Polymorphisms with Susceptibility to Cervical Carcinoma.

Background:In spite of substantial declines in both incidence and mortality rates in the past 50 years, cervical cancer remains one of the leading causes of cancer associated mortality among women globally. We performed this meta-analysis to explore the role of XRCC3 rs861539, MTHFR rs1801133, IL-6 rs1800795, IL-12B rs3212227, TNF-α rs1800629 and TLR9 rs352140 polymorphism with susceptibility to cervical carcinoma. Methods:The search databases include PubMed, SciELO, MedRxiv, Web of Science, Scopus, Cochrane Library, China National Knowledge Infrastructure, and China Biology Medicine disc up to 30 June 2021. The language is limited to English and Chinese. The comparison between the polymorphisms and cervical cancer was assessed using pooled odds ratio (OR) and 95% confidence interval (CI). The data are statistically analyzed by Comprehensive Meta-Analysis (CMA) 2.0 software. Results:A total of 59 studies including seven studies with 1,112 cases and 1,233 controls on XRCC3 rs861539, 14 studies with 2,694 cases and 3349 controls MTHFR rs1801133, four studies with 1,121 cases and 1,109 controls on IL-12B rs3212227, seven studies with 1,452 cases and 2,186 controls on IL-6 rs1800795, 20 studies with 4,781 cases and 4909 controls on TNF-α rs1800629, and seven studies with 1743 cases and 2292 controls on TLR9 rs352140 were included. There was a significant association between XRCC3 RS861539, TNF-α rs1800629, and IL-6 rs1800795 polymorphisms and an increased risk of cervical carcinoma in overall population. However, the MTHFR rs1801133, IL-12B rs3212227 and TLR9 rs352140 polymorphisms were not associated. Conclusion:The pooled analysis showed that XRCC3 RS861539, TNF-α rs1800629, and IL-6 rs1800795 were associated with cervical carcinoma susceptibility, but not MTHFR rs1801133, IL-12B rs3212227 and TLR9 rs352140 polymorphisms.

Interleukin-1 and Interleukin-6 Polymorphisms Might Influence Predisposition to Hemorrhagic Cerebral Vascular Diseases: A Meta-Analysis

Background: Interleukin-1 (IL-1) and IL-6 polymorphisms might influence predisposition to hemorrhagic cerebral vascular diseases, but the results of already published studies regarding relationship between IL-1/IL-6 polymorphisms and hemorrhagic cerebral vascular diseases were still controversial and ambiguous. Objectives: The authors designed this meta-analysis to more precisely estimate the relationship between IL-1/IL-6 polymorphisms and hemorrhagic cerebral vascular diseases by pooling the results of already published related studies. Methods: The authors searched PubMed, EMBASE, Web of Science, and CNKI for already published studies. Eighteen already published studies were pooled analyzed in this meta-analysis. Results: The pooled meta-analyses’ results showed that distributions of IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms among patients and controls differed significantly. Moreover, distribution of the IL-6 rs1800795 polymorphism among patients and controls from Asians also differed significantly. Further analyses showed similar findings for IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms in aneurysmal subarachnoid hemorrhage (aSAH) subgroup. Conclusions: This meta-analysis suggested that IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms might influence susceptibility to hemorrhagic cerebral vascular diseases, especially for aSAH. Moreover, IL-6 rs1800795 might influence susceptibility to hemorrhagic cerebral vascular diseases in Asians.

Dietary Acid Load and Its Interaction with IGF1 (rs35767 and rs7136446) and IL6 (rs1800796) Polymorphisms on Metabolic Traits among Postmenopausal Women.

The objective of this study was to explore the effects of dietary acid load (DAL) and IGF1 and IL6 gene polymorphisms and their potential diet–gene interactions on metabolic traits. A total of 211 community-dwelling postmenopausal women were recruited. DAL was estimated using potential renal acid load (PRAL). Blood was drawn for biochemical parameters and DNA was extracted and Agena® MassARRAY was used for genotyping analysis to identify the signalling of IGF1 (rs35767 and rs7136446) and IL6 (rs1800796) polymorphisms. Interactions between diet and genetic polymorphisms were assessed using regression analysis. The result showed that DAL was positively associated with fasting blood glucose (FBG) (β = 0.147, p < 0.05) and there was significant interaction effect between DAL and IL6 with systolic blood pressure (SBP) (β = 0.19, p = 0.041). In conclusion, these findings did not support the interaction effects between DAL and IGF1 and IL6 single nucleotide polymorphisms (rs35767, rs7136446, and rs1800796) on metabolic traits, except for SBP. Besides, higher DAL was associated with higher FBG, allowing us to postulate that high DAL is a potential risk factor for diabetes.

Evaluation of IL1B rs1143634 and IL6 rs1800796 Polymorphisms with Autism Spectrum Disorder in the Turkish Children

ABSTRACT Background Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder caused by genetic, environmental and immunological factors. It is known that neural development processes are affected by immune functions. The aim of this study is to evaluate the relationship between cytokines IL6 and IL1B gene polymorphisms in ASD. Methods DNA isolations were performed in 95 children diagnosed with ASD and 84 unrelated healthy children, single-nucleotide changes in IL6 (rs1800796) and IL1B (rs1143634) genes were determined by using Real-Time PCR (Real-Time Polymerase Chain Reaction) method. Results IL6 rs1800796 polymorphism presented an elevated risk for the development of ASD with CG genotype and dominant model (CG+GG vs. CC), CG+GG carriers (OR = 1.867, p = 0.057; OR = 1.847, p = 0.055, respectively). CT genotype in IL1B rs1143634 polymorphism associated with 2.33 times elevated risk of autism and showed a significant association compared to wild-type CC genotype (p = 0.02). IL1B rs1143634 polymorphism presented a significantly elevated risk for the development of ASD with recessive model (CC+CT vs.TT), TT genotype (OR = 8.145, p = 0.02). Conclusion This study concludes that rs1143634 is associated with the risk of ASD in Turkish children. Determining these polymorphisms in a larger sample group may contribute to understanding the etiology of ASD and developing new treatment protocols. Abbreviations ASD: Autism spectrum disorder; DNA: Deoxyribonucleic acid; IL6: Interleukin 6; IL1B: Interleukin 1 beta; Real-time PCR: Real-time polymerase chain reaction; JAK-STAT: The Janus kinase/signal transducers and activators of transcription; MAPK: The mitogen-activated protein kinase; 5ʹUTR: The 5′ untranslated region; IL1α: Interleukin 1 alpha; IL-1Ra: Interleukin 1 receptor antagonist; NF-κB: Nuclear factor-kappa B; DSM-V: The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; M-CHAT: Modified Checklist for Autism in Toddlers; EDTA: Ethylenediaminetetraacetic acid; gDNA: Genomic DNA; HWE: Hardy–Weinberg equilibrium; ANK2: Ankyrin 2; NL3: Neuroligin-3; XRCC4: X-ray repair cross complementing 4

Associations between Gene Polymorphisms in Pro-inflammatory Cytokines and the Risk of Inflammatory Bowel Disease: A Meta-analysis

ABSTRACT The relationships between polymorphisms in pro-inflammatory cytokines and the risk of inflammatory bowel disease (IBD) remain discrepant. Therefore, the authors conducted a meta-analysis to robustly explore relationships between polymorphisms in pro-inflammatory cytokines and the risk of IBD by integrating the results of previous works. Medline, Embase, Wanfang, VIP and CNKI were searched throughly for eligible studies, and 35 genetic association studies were finally included in this meta-analysis. We noticed that genotypic frequencies of IL-1B rs1143627, IL-6 rs1800795 and IL-8 rs4073 polymorphisms among cases with IBD and population-based controls differed significantly. Moreover, we found that genotypic frequencies of IL-1B rs1143627 and IL-6 rs1800795 polymorphisms among cases with IBD and population-based controls of Caucasian origin differed significantly, whereas genotypic frequency of IL-8 rs4073 and IL-18 rs187238 polymorphisms among cases with IBD and population-based controls of Asian origin also differed significantly. Furthermore, we also noticed that genotypic frequency of IL-18 rs187238 polymorphism among cases with Crohn’s disease (CD) and population-based controls differed significantly. In conclusion, this meta-analysis demonstrated that IL-1B rs1143627 and IL-6 rs1800795 polymorphisms were significantly associated with the risk of IBD in overall population and Caucasians. Moreover, IL-8 rs4073 polymorphism was significantly associated with the risk of IBD in overall population and Asians. In addition, we also noticed that IL-18 rs187238 polymorphism was significantly associated with the risk of CD, and IL-18 rs1946518 polymorphism was significantly associated with the risk of IBD in Asians.