Interleukin-6 Rs1800795 Research Articles

Male adolescents with Interleukin 10 rs1800872 AA genotype had higher prevalence and slower recoveries of post-traumatic stress disorder at late stage of a follow-up

BackgroundPathophysiological mechanisms of post-traumatic stress disorder (PTSD) are elusive and heterogeneous relationships have been reported among PTSD, Interleukin 10 (IL-10), and other factors after stresses. The present study aimed to longitudinally investigate associations of PTSD with environmental factors and genetic variation of rs1800872 at IL-10 gene. MethodsSymptoms of PTSD were measured by PTSD Checklist-Civilian Version (PCL-C) in 462 high school students at 6, 12, and 18 months after Wenchuan earthquake in China. Genotypes of IL-10 rs1800872 were identified by polymerase chain reaction-restriction fragment length polymorphism analysis and verified by DNA sequencing. ResultsAA homozygotes had higher PTSD prevalence than C allele carriers only at 18 months in male, but not female subjects. PTSD prevalence at 18 months was lowered in all subjects except male AA homozygotes when compared to that at 6 months, and only in female C allele carriers when compared to that at 12 months. PCL-C scores at 18 months were decreased in all students but not in male AA homozygotes when compared to those at 6 months. IL-10 rs1800872 was associated with PTSD at 18 months. Patterns of predictors of PCL-C scores were different between AA homozygotes and C allele carriers at different times during the follow-up. ConclusionThere were different reciprocal actions of IL-10 rs1800872 with other potential factors or predictors on PTSD in a time-course and gender-dependent manner. Male students with IL-10 rs1800872 AA genotype had higher prevalence and slower recoveries of PTSD at late stage of the follow-up, suggesting requirements of special psychiatric care or drug supplementation at this stage.

The Determination of IL-6 rs1800795 Polymorphism Distribution in Turkish National Cross-Country Skiing Athletes Sub-groups Created Referring to the 1km CCSTAs

Objective: Interleukin-6 (IL-6) is an effective and functional protein with a cytokine structure. IL-6 is effective in the immune system like a pro/anti-inflammatory response, and muscle tissue hypertrophy and repair. Our study aimed to investigate the IL-6 rs1800795 polymorphism distribution in Turkish National Cross-Country Skiing Athletes and to determine the advantageous genotype for endurance performance. 
 Methods: 34 athletes within 3 groups; General (Group-1), Women (Group-2), and Men (Group-3) were enrolled to the study. Also each groups were divided into sub-groups according to their “1-kilometer cross-country average skiing-times (1 km-CCSTAs)”. Blood samples were used for DNA isolation and genotyping were completed by real time- PCR. 
 Results: The groups' 1 km-CCSTAs were 188.7 ± 22.4, 212.3 ± 17.8, and 177.4 ± 14.1 seconds, respectively. We detected the genotypes as 17 GG (50%) and 17 GC (50%) in Group-1; 5 GG (45%) and 6 GC (55%) in Group-2; 12 GG (52%) and 11 GC (48%) in Group- 3. We detected no CC genotype in groups. Chi-square Fisher’s test was used for statistical analysis. 
 Conclusion: An increased GC genotype ratio was detected in the faster sub-groups of each group compared to the slower sub-groups. But we obtained the significant genotype distribution only in Group-3 (p

IL-6 Polymorphisms Are Not Related to Obesity Parameters in Physically Active Young Men.

Interleukin 6 (IL-6) is a cytokine with both pro- and anti-inflammatory actions, but is also considered as a “metabolic hormone” involved in immune responses, affecting glucose, protein and lipid metabolism. It has been proposed to be related to obesity, but various results have been presented. Thus, in this study, the very homogenous population of young, male military professionals, living in the same conditions involving high physical activity, has been selected to avoid the influence of environmental factors. The subjects were divided into groups depending on the obesity parameters BMI (body mass index) and fat percentage (fat%), and the following IL-6 SNPs (Single Nucleotide Polymorphisms) were analyzed: rs1800795, rs1800796 and rs13306435. No relation was found between obesity parameters and IL-6 polymorphisms rs1800795, rs1800796 and rs13306435. It may be postulated that even if a genetic predisposition involves IL-6 genes, this effect in individuals with obesity of a low grade is minor, or can be avoided or at least markedly reduced by changes in lifestyle.

Smoking, Hypertension, and GG Genotype of the IL-6 rs1800796 Polymorphism are Independent Risk Factors for Abdominal Aortic Aneurysm in Han Population

BackgroundRecent researches have investigated the link between the rs1800796 polymorphism (−572G/C) in the interleukin-6 (IL-6) gene and the risk of abdominal aortic aneurysm (AAA). However, no Chinese studies have addressed the association between the risk of AAA and this polymorphism.MethodsThis case-control study included 153 AAA patients and 205 controls. Diabetes mellitus, hypertension, dyslipidemia, and coronary artery disease (CAD) status were collected. The AAA and control groups were 69.20 ± 7.56 and 68.50 ± 7.12 years old, respectively.ResultsThe analysis revealed that the G allele and GG genotype of the IL-6 rs1800796 polymorphism were remarkedly correlated with an elevated risk of AAA. The GG genotype displayed an association with the risk of AAA after adjustment for gender, body mass index, age, drinking, and smoking. Subgroup analyses indicated that this polymorphism elevated the risk of AAA among males, individuals aged ≥70 years, smokers, drinkers, individuals with a body mass index (BMI) ≥25 kg/m2, patients without diabetes, and patients with hypertension. Univariate and multivariate analyses indicated that smoking, hypertension, and the GG genotype (rs1800796 polymorphism) were independently related with the risk of AAA.ConclusionThe IL-6 rs1800796 polymorphism increases the risk of AAA. In addition, smoking, hypertension, and the GG genotype of the rs1800796 polymorphism are independent risk factors for AAA. Further studies of Chinese populations are needed to validate these findings.

Cytokine (IL-10, IL-6, TNF-α and TGF-β1) Gene Polymorphisms in Chronic Hepatitis C Virus Infection among Malay Male Drug Abusers.

Cytokines play an important role in modulating inflammation during viral infection, including hepatitis C virus (HCV) infection. Genetic polymorphisms of cytokines can alter the immune response against this infection. The objective of this study was to investigate the possible association between chronic hepatitis C virus infection susceptibility and cytokine gene polymorphism for interleukin-10 (IL-10) rs1800896 and rs1800871, interleukin 6 (IL-6) rs1800795, TNF-α rs1800629, and TGF-β1 rs1800471 in Malay male drug abusers. The study was conducted on 76 HCV-positive (HP) male drug abusers and 40 controls (HCV-negative male drug abusers). We found that there were significant differences in the frequencies of genotype for IL-10 rs1800871 (p = 0.0386) and at the allelic level for IL-10 rs1800896 A versus G allele (p = 0.0142) between the HP group and the control group. However, there were no significant differences in gene polymorphism in interleukin 6 rs1800795, TNF-α rs1800629 and TGF-β1 rs1800471. These findings suggest significant associations between gene polymorphism for IL-10 rs1800871, IL-10 rs1800896 (at the allelic level) and susceptibility to HCV infection among Malay male drug abusers.

Associations between Certain Polymorphisms in Proinflammatory Cytokines and Predisposition of Alzheimer’s Disease: A Meta-Analysis

Background: Functional gene polymorphisms of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-18 (IL-18) may contribute to the onset and development of Alzheimer’s disease (AD), but the relationships between these polymorphisms and predisposition of AD remain controversial. Objectives: This meta-analysis was conducted to more robustly assess relationships between TNF-α/IL-6/IL-8/IL-18 polymorphisms and predisposition of AD by pooling the findings of relevant studies. Methods: A comprehensive literature searching was performed in PubMed, Embase, Web of Science, Wanfang, and CNKI databases, and 63 studies were found to be eligible for quantitative analyses. Results: The pooled meta-analysis results showed that genotypic frequencies of TNF-α rs1800629, IL-6 rs1800795, IL-8 rs4073, and IL-18 rs187238 polymorphisms among AD cases and controls of Asian ethnicity differed significantly. But, we did not observe such genotypic frequencies differences in Caucasians. Conclusions: This meta-analysis suggests that TNF-α rs1800629, IL-6 rs1800795, IL-8 rs4073, and IL-18 rs187238 polymorphisms may affect predisposition of AD in Asians, but not in Caucasians.

Interleukin 6 (rs1800795) and pentraxin 3 (rs2305619) polymorphisms-association with inflammation and all-cause mortality in end-stage-renal disease patients on dialysis

Chronic inflammation plays an important role in the progression and outcome of chronic kidney disease (CKD). The circulating levels of the inflammatory biomarkers interleukin 6 (IL6) and pentraxin 3 (PTX3) are enhanced in CKD patients, and are associated with the progression of the disease and with higher risk for cardiovascular events, the major cause of death in CKD patients. Our aim was to study how specific polymorphisms of IL6 and PTX3 encoding genes affect the inflammatory response and outcome of end-stage renal disease (ESRD) patients on dialysis. Methodology included the analysis of two single nucleotide polymorphisms (SNP), namely the IL6 (rs1800795) polymorphism in the promoter region (-174G > C), and the PTX3 (rs2305619) polymorphism in the intron 1 (+ 281A > G), which were analyzed in ESRD patients on dialysis and in a group of heathy individuals. The allelic frequencies, genotype distribution and their association with circulating levels of the inflammatory markers C-reactive protein (CRP), IL6, growth differentiation factor 15 (GDF15) and PTX3, were determined in ESRD patients. Events of death were recorded along one year, to assess the association of the studied SNPs with all-cause mortality and the inflammatory biomarkers, in ESRD patients. Results showed that the allelic frequencies and genotype distribution for IL6 and PTX3 SNPs in the control group and ESRD patients were similar and in agreement with other European reports. For the IL6 polymorphism, we found a trend towards higher levels of high-sensitivity (hs) CRP, IL6 and PTX3 in the homozygous genotypes; the CC genotype also showed the highest levels of GDF15. The mortality rate after the 1-year follow-up was 10.4%. The CC genotype (IL6 SNP) was associated to a higher risk of mortality and deceased patients carrying this genotype also showed the highest levels of hsCRP. Regarding the studied PTX3 SNP, the AA genotype was linked to an enhanced inflammatory response, showing the highest values of hsCRP and IL6. Nevertheless, this genotype had no significant impact on the mortality rate. In conclusion, both studied SNPs seem to modulate the inflammatory response in ESRD and may, therefore, be determinant on disease progression and patients’ outcome. Our data also highlights the importance of research on genetic variants that, although less frequent, may have significant biological value.

MO810INTERLEUKIN-6 (-174G/C) POLYMORPHISM, RS1800795, IN ESRD PATIENTS' OUTCOME*

Abstract Background and Aims Chronic inflammation plays an important role in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). The single nucleotide polymorphism (SNP) in the promoter region (-174G/C) of interleukin-6 (IL6) gene regulates the levels of this cytokine, which have been associated with a poor outcome in several pathologies. Our aims were to determine, according to the genotype distribution of this polymorphism, the association between the inflammatory mediators, high sensitivity C-reactive protein (hsCRP), IL6, and pentraxin 3 (PTX3), shown to be increased in ESRD, and to estimate the risk for all-cause mortality over a period of one year. Method 289 ESRD patients on hemodialysis (high-flux hemodialysis and hemodiafiltration) were included in this study. Real-Time PCR TaqMan SNP genotyping assays were used to assess allelic frequencies of IL6 (rs1800795). We evaluated the circulating levels of PTX3, hsCRP and IL6 using commercially available kits. Deaths occurring along 1-year follow-up period were recorded, and the all-cause mortality hazard ratio (HR), according to IL6 polymorphisms in this patient cohort were determined by Cox regression analysis. A p < 0.05 value was considered statistically significant. Results In all IL6 (-174G>C) genotypes, hsCRP was positively and significantly correlated with IL6. For hsCRP and PTX3, a positive correlation with significance was only found for the GG genotype. All genotypes showed positive correlations between IL6 and PTX3 circulating levels, although only the GG genotype achieved a significant value. The Cox regression survival analysis for all-cause mortality in ESRD patients, using as reference the heterozygous patients for IL6 polymorphism, showed that CC patients presented a significant higher mortality risk, with a HR of 3.275 [1.165 to 9.204]. Moreover, the median survival time of CC patients (100 [54 - 138] days) was lower than that presented by the GG genotype patients (211 [83 - 290] days, p < 0.05 vs. CC) and by the heterozygous patients (291 [72 - 332] days, p = 0.157 vs. CC). Conclusion We observed different correlation profiles between inflammatory biomarkers within each IL6 (-174G>C) genotype. The association of the CC genotype of the IL6 polymorphism with a poorer outcome and shorter survival time for ESRD patients was also observed. However, further studies are required and must consider the underlying individual genetic background, since the inflammatory state appears to be influenced by IL6 polymorphisms, which, in turn, might be determinant for disease progression and outcome. Acknowledgments This work was supported by Applied Molecular Biosciences Unit-UCIBIO, financed by national funds from FCT/MCTES (UIDB/04378/2020), by North Portugal Regional Coordination and Development Commission (CCDR-N)/NORTE2020/Portugal 2020 (Norte-01-0145-FEDER-000024) and by REQUIMTE-Rede de Química e Tecnologia-Associação in the form of a researcher (S. Rocha) – project Dial4Life co-financed by FCT/MCTES (PTDC/MEC-CAR/31322/2017) and FEDER/COMPETE 2020 (POCI-01-0145-FEDER-031322).

Polymorphisms and haplotypes of IL2RA, IL10, IFNG, IRF5, and CCR2 are associated with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in children.

Cytokine storms are central to the development of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH). Previous studies have shown that single-nucleotide polymorphisms (SNPs) of cytokine genes may be associated with the development of EBV-HLH in children. As such, we investigated the association between susceptibility to EBV-HLH in children and SNPs and haplotypes of genes encoding interleukin-2 receptor subunit alpha (IL2RA), interleukin-10 (IL10), interferon gamma (IFNG), interferon regulatory factor 5 (IRF5), and C-C chemokine receptor 2 (CCR2). Sixty-six children with EBV-HLH and 58 healthy EBV-seropositive controls were enrolled in this study. SNPs of IL2RA rs2104286, rs12722489, and rs11594656; IL10 rs1800896, rs1800871, and rs1800872; IFNG rs2430561, IRF5 rs2004640, and CCR2 rs1799864 were assayed and genotyped using the SNaPshot technique. Frequencies of the A allele of IL2RA rs2104286 and IL10 rs1800896, and C allele of IL-10 rs1800872 were significantly higher in the EBV-HLH group than in the control group. The AA genotype of IL2RA rs2104286 and IL10 rs1800896, and the CC genotype of IL10 rs1800872 might be associated with a significantly high risk of EBV-HLH. However, the frequencies of genotypes and alleles of IL2RA rs2104286, IL10 rs1800871, IFNG rs2430561, IRF5 rs2004640, and CCR2 rs1799864 were similar in both groups. Additionally, IL2RA AGT (rs2104286-rs12722489-rs11594656) and IL10 ACC (rs1800896-rs1800871-rs1800872) haplotypes were also associated with an increased risk of EBV-HLH. SNPs of IL2RA rs2104286, IL10 rs1800896 and rs1800872 and the haplotypes of IL2RA AGT and IL10 ACC were highly associated with susceptibility to EBV-HLH in children.

Association of xenobiotic-metabolizing enzymes (GSTM1 and GSTT 1), and pro-inflammatory cytokines (TNF-α and IL-6) genetic polymorphisms with non-alcoholic fatty liver disease.

Previous studies have revealed that genetic polymorphisms of the Glutathione S-transferase M1 and T1 (GSTM1 and GSTT1), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) are associated with the presence of non-alcoholic fatty liver disease (NAFLD) in many populations. This study was conducted to investigate the association of the GSTM1, GSTT1, TNF-α rs1800629, and IL-6 rs1800795 with NAFLD in the general Iranian population. A case-control analysis included 242 NAFLD patients and 324 healthy controls from Iranian adults. After the physical examination, the genotypes were determined by polymerase chain reaction(PCR). The GSTM1 null, GSTT1 null, TNF-α AG/AA, and IL-6 CG/CC genotypes were deemed to be high-risk. The null allele of GSTM1 and A allele of TNF-α were more frequent in NAFLD patients even after Bonferroni's correction (P values<0.005, adjusted odds ratio (OR), 1.66 and 2.02; 95% confidence intervals (CI), (1.18-2.32) and (1.34-3.34), respectively. The IL-6 CC/CG genotype association with NAFLD was not significant after correction (P value = 0.04) Polymorphisms of xenobiotic and pro-inflammatory genes are associated with NAFLD in the Iranian population and seem to be a useful tool for NAFLD prevention and care.

Genetic Association of Interleukin-6 Polymorphism (rs1800796) with Chronic Hepatitis B Virus Infection in Chinese Han Population.

Hepatitis B virus (HBV) infection is a global health care burden that can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. We conducted this study to identify the association between interleukin-6 (IL-6) gene rs1800796 (-572G/C) polymorphism and the risk of chronic HBV infection in adults. A total of 1,048 participants including 518 cases and 530 controls were recruited for this study. The Mass Array time-of-flight mass spectrometer was applied for single-nucleotide polymorphism rs1800796 genotyping. There was a significant correlation between genotype CG in rs1800796 and chronic HBV infection in the Chinese Han population (odds ratio [OR] = 0.759, 95% confidence interval [CI]: 0.586-0.983, p = 0.04), which was also observed at allele G (OR = 0.800, 95% CI: 0.657-0.975, p = 0.02). Furthermore, significant differences in the ≤45 years old group (CC vs. CG+GG, OR = 0.616, 95% CI: 0.413-0.918, p = 0.02) and in the male group (CC vs. CG+GG, OR = 0.666, 95% CI: 0.483-0.920, p = 0.01) were found in the subgroups analysis. Our data revealed a significant association of IL-6 rs1800796 with the risk of chronic HBV infection in the Chinese Han population; meanwhile, age and gender are two coordinative risk factors, which provides new clues for the study of susceptibility of chronic HBV infection in adults.

The single nucleotide polymorphisms of interleukin-10 are associated with the risk of leukaemia: Evidence from 18 case-control studies.

Interleukin-10(IL-10) is an immunosuppressive cytokine and plays an important role in inflammation and cancers. Numerous studies have explored the association between single nucleotide polymorphisms of IL-10 and leukemia, but their results were conflicting, so we performed this meta-analysis to elucidate the association between 3 common single nucleotide polymorphisms of IL-10 (rs1800896, rs1800871 and rs1800872) and risk of leukemia.We conducted a comprehensive research in Pubmed, Chinese Biomedical Literature Database disc and Embase using related terms. After strict selection, 18 studies with 2264 cases and 3846 controls were included into this meta-analysis. Odds ratio and 95% confidence interval were used to evaluate the strength of the association.We found that polymorphism of IL-10 -1082A/G was associated with decreased risk of leukemia both in overall analysis and in stratified analysis according to ethnicity and cancer type. A strong relationship was also uncovered between polymorphism of IL-10 -592C/A and increased risk of leukemia in non-Chinese.GG genotype of IL-10 -1082A/G is associated with decreased risk of leukemia, especially chronic lymphocytic leukemia. CC genotype of -592C/A is associated with decreased risk of leukemia in non-Chinese.

Association between TH2 Cytokine Gene Polymorphisms and Risk of Bullous Pemphigoid

ABSTRACT Background T-helper 2 (Th2)-associated cytokines are involved in the pathogenesis of bullous pemphigoid (BP), an autoimmune skin disease. Increased expression of Th2 cytokines such as interleukin-4 (IL-4), IL-5, IL-6, IL-10, and IL-13 have been observed in serum, skin biopsies and/or blister fluid. This study aimed to uncover a possible association between Th2 cytokine genetic variations and susceptibility to BP. Methods In a cohort study, blood samples of BP patients and controls were obtained and variations in IL-4 (rs2243250 and rs2070874), IL-4R (rs1805010), IL-5 (rs2069812), IL-6 (rs1800795), IL-10 (rs1800896, rs1800871, and rs1800872), and IL-13 (rs1800925 and rs20541) were genotyped by PCR-RFLP assays. Furthermore, quantitative expression levels of IL-13 gene were evaluated by real-time RT-PCR analysis. Results Among the studied variations, a significantly higher frequency of the C-allele was observed in IL-13 gene variation (rs1800925) in the healthy individuals than BP patients. This may indicate a protective effect of C-allele on predisposition to BP. Considering individuals carrying polymorphic genotypes compared to wild genotype, the minor G-allele of IL-4R rs1805010 and A-allele of IL-13 rs20541 had a promotive and protective effect, respectively, on predisposing to the development of BP. No significant difference in IL-13 mRNA expression was detected between BP patients and healthy individuals. Conclusions Our results indicate that IL-13 rs1800925 variation may be a protective genetic marker for the development of BP. Given this preventive effect against BP, therapeutic strategies could potentially be developed interfering with the functions of IL-13 cytokine, which seems to be integral in the pathogenesis of eosinophilic inflammatory disorders, such as BP.

Association of the IL-6 Rs1800796 SNP with Concentration/dose Ratios of Tacrolimus and Donor Liver Function after Transplantation

ABSTRACT Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a range of important roles such as in inflammation, immune response, and cell growth regulation. Here, we aimed to assess the potential influence of the IL-6 single nucleotide polymorphism (SNP) rs1800796 on the concentration/dose (C/D) ratios of tacrolimus and donor liver function in Chinese liver transplant patients. A total of 331 liver transplant patients were included in this study. The C/D ratios and the ALT, AST, T-BIL, ALP, and GGT levels were analyzed at different time points in patients with and without the IL-6 rs1800796 SNP. The IL-6 rs1800796 polymorphism in recipients was found to be correlated with the C/D ratios of tacrolimus at months 2 to month 6 after transplantation. Also, the rs1800796 SNP in donors was found to influence liver function (shown in the data of ALT, AST, T-BIL, ALP and GGT) in recipients at the early post-transplant stage after transplantation. In conclusion, the IL-6 rs1800796 polymorphism was associated with the C/D ratios of tacrolimus and post-transplant donor liver function.

Relationship between interleukin-13 rs20541 single nucleotide polymorphisms and therapeutic efficacy in children with asthma.

ObjectiveTo investigate the relationship between therapeutic efficacy in children with asthma and interleukin-13 (IL-13) rs20541 polymorphisms.MethodsFifty children with moderate-to-severe asthma were assigned to the GG, GA, and AA groups according to the IL-13 gene locus rs20541 polymorphism. The patients received budesonide inhalation suspension 1 mg twice daily combined with fluticasone propionate 80 µg/inhalation. The improvement of clinical symptoms (gasping, coughing, and wheezing), improvement of lung function, and adverse reactions were observed.ResultsLung function did not significantly differ among three groups before treatment. After treatment, the time to symptom relief was significantly shorter in the GG group than that in the other two groups. The forced expiratory volume in one second and percent predicted peak expiratory flow were also significantly better in the GG group than in the other two groups.ConclusionBudesonide inhalation suspension combined with fluticasone propionate is an effective treatment regimen for moderate-to-severe asthma. Polymorphism of the IL-13 rs20541 locus may be correlated with therapeutic efficacy. Patients carrying the GG allele were more responsive than their counterparts with the GA or AA allele.

Gene polymorphisms of pro-inflammatory cytokines may affect the risk of Graves' disease: a meta-analysis.

Gene polymorphisms of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) may influence the risk of Graves' disease, but the results of so far published studies remain inconclusive. Therefore, the authors conducted this meta-analysis to assess relationships between TNF-α/IL-1/IL-6 polymorphisms and the risk of Graves' disease by pooling the findings of all relevant studies. A comprehensive literature searching of Pubmed, Embase, Web of Science and CNKI was conducted by the authors, and twenty-eight studies were found to be eligible for pooled analyses. The pooled meta-analyses results showed that genotypic frequencies of TNF-α rs1800629, IL-1A rs1800587, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms among patients with Graves' disease and control subjects differed significantly. Moreover, we found that genotypic frequencies of TNF-α rs1800629 and IL-6 rs1800795 polymorphisms among patients with Graves' disease and control subjects in Caucasians differed significantly, and genotypic frequencies of IL-1A rs1800587, IL-1B rs16944, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms among patients with Graves' disease and control subjects in Asians also differed significantly. Nevertheless, we did not detect such genotypic frequencies differences for TNF-α rs361525 and IL-1B rs1143627 polymorphisms. This meta-analysis suggests that TNF-α rs1800629, IL-1A rs1800587, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms may influence the risk of Graves' disease in overall population. Moreover, TNF-α rs1800629 and IL-6 rs1800795 polymorphisms may influence the risk of Graves' disease in Caucasians, while IL-1A rs1800587, IL-1B rs16944, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms may influence the risk of Graves' disease in Asians.

Effects of gene polymorphism and serum levels of IL-2 and IL-6 on endometriosis.

EMT is closely related to gene polymorphism and the expression level of immune-related substances in patients. Therefore, the aim of this study was to investigate the relationship between single nucleotide polymorphism (SNP), as well as serum levels of interleukin 2 (IL-2) and interleukin 6 (IL-6) in patients with endometriosis (EMT) and disease susceptibility. Peripheral blood of EMT patients and healthy people were collected, respectively. Genomic deoxyribonucleic acid (DNA) was extracted and sequenced to obtain gene polymorphisms of IL-2 rs11575812 (T>C), rs2069772 (A>G), rs2069762 (T>G), and IL-6 rs1800795 (C>G). Meanwhile, the serum levels of IL-2 and IL-6 were determined by the relative kits. For IL-2 rs11575812 allele (C>G), the odds ratio (OR) was 0.49, the 95% confidence interval (CI) was 0.37-0.66, and the p-value was 0. For IL-2 rs2069772 allele (C>G), the OR was 0.97, the 95% CI was 0.73-1.27, and the p-value was 0.83. For IL-2 rs2069762 allele (T>G), the OR was 1.73, the 95% CI was 1.31-2.29, and the p-value was 0. For IL-6 rs1800795 allele (C>G), the OR was 1.26, the 95% CI was 0.96-1.66, and the p-value was 0.09. CC genotype (p=0.000) and TT genotype (p=0.040) of IL-2 rs11575812 (T>C), AG genotype (p=0.000) of IL-2 rs2069772 (A>G), and GT genotype (p=0.000) of rs2069762 (T>G) were remarkably associated with the serum level of IL-2 in patients with EMT. Similarly, the CG genotype (p=0.000) of IL-6 rs1800795 (C>G) was significantly correlated with the serum level of IL-6 in patients with EMT. IL-2 haplotype CAG (p=0.005), CAT (p=0.001), CGG (p=0.047), TAG (p=0.000), and TGG (p=0.000) were significantly different from other haplotypes. Furthermore, there was a significant correlation between the serum levels of IL-2 and IL-6 (r=0.63, p<0.001). IL-2 rs11575812 (T>C) TT genotype, rs2069772 (A>G) AG genotype and rs2069762 (T>G) GG genotype increases the risk of EMT, which are related to the serum levels of IL-2 and IL-6.

IL-10, IL-18 Gene Polymorphisms Might Influence Predisposition to Coronary Artery Disease in East Asians: A Meta-Analysis

ABSTRACT The results of already published studies regarding relationship between interleukin-10 (IL-10), interleukin-18 (IL-18) polymorphisms and predisposition to coronary artery disease (CAD) were still controversial. So the authors designed this meta-analysis to more precisely estimate relationship between IL-10, IL-18 polymorphisms and CAD by pooling the results of already published studies. The authors searched Pubmed, Embase, Web of Science and CNKI for already published studies. The authors used Review Manager to pool the results of already published studies. Thirty-four studies were pooled analyzed in this meta-analysis. The pooled meta-analyses results showed that IL-18 rs187238, IL-18 rs1946518 and IL-18 rs1946519 polymorphisms were all significantly associated with predisposition to CAD in the general population. We also detected similar significant results for IL-10 rs1800871, IL-10 rs1800896, IL-18 rs187238 and IL-18 rs1946518 polymorphisms in East Asians in further subgroup analyses. In conclusion, this meta-analysis suggested that IL-10 rs1800871, IL-10 rs1800896, IL-18 rs187238 and IL-18 rs1946518 polymorphisms might influence predisposition to CAD in East Asians.

Associations between Seven Common Cytokine Gene Polymorphisms and Coronary Artery Disease: Evidence from a Meta-Analysis

Background: Associations of polymorphisms in interferon-gamma (IFNG), interleukin-10 (IL-10), and interleukin-18 (IL-18) with coronary artery disease (CAD) have already been investigated by many studies, yet the findings of these studies have been somewhat inconsistent. Objectives: The aim of this meta-analysis was to better clarify associations between polymorphisms in IFNG/IL-10/IL-18 and CAD by combing the results of all relevant articles. Methods: Eligible articles were searched from PubMed, EMBASE, WOS, and CNKI. We used Review Manager to combine the results of indi­vidual studies. Results: Fifty-one studies were included in this meta-analysis. Combined results revealed that IFNG rs243056, IL-10rs1800871, IL-18rs187238, IL-18rs1946518, and IL-18rs1946519 polymorphisms were all significantly associated with CAD in the general population. We also obtained similar significant results for IFNG rs243056, IL-10rs1800871, IL-10 rs1800896, IL-18rs187238, IL-18rs1946518, and IL-18rs1946519 polymorphisms in Asians in further subgroup analyses. Conclusions: Collectively, this meta-analysis proved that IFNG rs243056, IL-10rs1800871, IL-10 rs1800896, IL-18rs187238, IL-18rs1946518, and IL-18rs1946519 polymorphisms may confer susceptibility to CAD for Asians.

Associations between genetic polymorphisms in interleukin-10 and hematological oncology: evidence from a meta-analysis

ABSTRACT Background Associations between polymorphisms in interleukin-10 (IL-10) and hematological oncology were already explored by many genetic association studies, with controversial findings. The aim of this meta-analysis was to more comprehensively analyze associations between polymorphisms in IL-10 and hematological oncology by combing the results of all relevant studies. Methods Eligible articles were searched from Pubmed, Embase, WOS and CNKI. The latest literature searching update was performed on 8 October 2019. We used Review Manager to combine the results of eligible studies. Results Forty-one articles were included in this meta-analysis. IL-10 rs1800890 polymorphism was found to be significantly associated with hematological oncology under AA vs. TT+TA (recessive comparison, OR = 1.12, 95% CI 1.02–1.24), and rs1800896 polymorphism was also found to be significantly associated with hematological oncology under AA vs. AG+GG (dominant comparison, OR = 0.89, 95% CI 0.83–0.95) in overall combined analyses. In subgroup analyses, we observed positive results for rs1800871 (recessive comparison), rs1800872 (dominant, recessive and allele comparisons), and rs1800896 (dominant and allele comparisons) polymorphisms in the non-Hodgkin’s lymphoma (NHL) subgroup. Besides, we also detected positive associations between rs1800872 polymorphism and acute leukemia (AL) (dominant and recessive comparisons) and found significant associations between rs1800896 polymorphism and chronic leukemia (CL) (recessive comparison). Conclusion In summary, this meta-analysis demonstrated that IL-10 rs1800890, rs1800896, rs1800871 and rs1800872 polymorphisms may confer susceptibility to hematology oncology, especially for NHL.