IL-10 Gene Polymorphisms Research Articles

Association between IL-18 gene polymorphisms and Hashimoto thyroiditis.

Hashimoto's thyroiditis (HT), which is also called lymphocytic thyroiditis, is the most frequent autoimmune thyroid disease (AITD), in which T helper-1 lymphocytes mediate the disease. IL-18 is expressed in thyroid follicular cells (TFCs) during HT. The findings of studies aimed at investigating the relationship between IL-18 and HT are highly contradictory. In this study, we aimed to investigate the association between IL-18 gene polymorphisms and HT. The study included 97 patients diagnosed with HT and 86 volunteers in the healthy control group. The IL18-607C/A (rs1946518) and -137G/C (rs187238) genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. No significant difference in the mean age or sex was observed between the groups (p = 0.763 andp = 0.658, respectively). The -137 IL18 CG genotype was more frequent in HT patients than in controls. In HT patients, the risk of the IL-18 CG genotype was more than 2.237 times higher (OR 2.237%95 Cl 1.195-4.187, p = 0.039) than that of the G/G genotype. Additionally, the -607 AC genotype was more frequent in the control group than in the HT group (in individuals with the IL18 CG genotype). According to our results, the CG genotype might be a risk factor for HT. Conversely, there is a possibility that the AC genotype plays a protective role against the condition. However,further studies will contribute to new solutions by revealing the molecular and cellular mechanisms of HT.

Prevalence of Allelic and Genotypic Variants of Il4, Il10, Il12b and Tlr2 Gene Polymorphism in Patients with Chronic Polypoid Rhinosinusitis

Chronic polyposis rhinosinusitis (CPRS) is an important medical and social problem due to its prevalence, combination with other diseases (bronchial asthma, cystic fibrosis), prolonged recurrent course, which leads to a decrease in the quality of life and performance of patients. Bronchopulmonary, rhinogenic orbital and intracranial complications arising against the background of chronic sinusitis not only worsen the quality of life of patients, but also sometimes lead to long-term disability, and sometimes to disability. The results of our study demonstrated that the distribution of the genotypes of polymorphisms of all genes corresponded to the expected, i.e., in this case, the Hardy-Weinberg equilibrium is fulfilled in both groups. Both samples rs2243250 of the IL4 gene were characterized by high frequencies of the unfavorable C allele and the heterozygous T / C genotype, rs3212227 of the IL12B gene of the A allele and the heterozygous A / C genotype, rs1800895 592 C> A in the IL10 gene of the A, C alleles, and heterozygous C rs5743708 in the TLR2 gene of the C allele and the heterozygous C / T genotype, hence the high level of genetic variability of the studied genes.

Prevalence of Allelic and Genotypic Variants of Il4, Il10, Il12b and Tlr2 Gene Polymorphism in Patients with Chronic Polypoid Rhinosinusitis

Chronic polyposis rhinosinusitis (CPRS) is an important medical and social problem due to its prevalence, combination with other diseases (bronchial asthma, cystic fibrosis), prolonged recurrent course, which leads to a decrease in the quality of life and performance of patients. Bronchopulmonary, rhinogenic orbital and intracranial complications arising against the background of chronic sinusitis not only worsen the quality of life of patients, but also sometimes lead to long-term disability, and sometimes to disability. The results of our study demonstrated that the distribution of the genotypes of polymorphisms of all genes corresponded to the expected, i.e., in this case, the Hardy-Weinberg equilibrium is fulfilled in both groups. Both samples rs2243250 of the IL4 gene were characterized by high frequencies of the unfavorable C allele and the heterozygous T / C genotype, rs3212227 of the IL12B gene of the A allele and the heterozygous A / C genotype, rs1800895 592 C> A in the IL10 gene of the A, C alleles, and heterozygous C rs5743708 in the TLR2 gene of the C allele and the heterozygous C / T genotype, hence the high level of genetic variability of the studied genes.

Analysis of propensity score matching between inflammatory factor levels and gene polymorphisms and susceptibility to obstructive sleep apnea

Objective:To explore the correlation between the levels of inflammatory factors and their gene polymorphisms and the susceptibility to obstructive sleep apnea（OSA）. Methods:Seventy-nine patients who were diagnosed with OSA in People's Hospital of Xinjiang Uygur Autonomous Region from October 2018 to December 2020 were selected as the study group, and 104 healthy adults who received physical examination during the same period were selected as the control group. After collecting the clinical data of the two groups of patients, the two groups of patients were matched by propensity scores. Then, the serum IL-6, IL-8 and TNF-α levels and the peripheral blood IL-6, IL-8 and TNF-α gene polymorphism analysis and comparison were performed on the included matched patients. Results:Before matching, the age, proportion of males, BMI, neck circumference, smoking history, SBP and DBP of the study group were higher than those of the control group, and the difference was statistically significant（P<0.05）. After the two groups of patients were matched by propensity scores, a total of 67 patients were successfully matched. The covariates between the two groups were all balanced after matching, and the balance of the PSM covariates was significantly improved（P>0.05）. After matching, the fasting blood glucose, C-reactive protein, IL-6, IL-8, TNF-α, AHI and Ts90% of the study group were significantly higher than those of the control group, and the difference was statistically significant（P<0.05）. Hardy-Weinberg balance verifies that the gene frequencies of each group are in accordance with the genetic balance rule（P>0.05）; after matching, the distribution of IL-6（rs1800795） and TNF-α（rs1800629） genotypes between the two groups is compared, and the difference is statistically significant scientific significance; the frequency of IL-6（rs1800795） allele C and the frequency of TNF-α（rs1800629） allele A in the study group were significantly higher than those in the control group, and the difference was statistically significant（P<0.05）. Conclusion:The levels of inflammatory factors TNF-α and IL-6 and their gene polymorphisms are significantly related to the susceptibility to OSA.

Interleukin-6 gene polymorphism in Saudi population with recurrent aphthous stomatitis

IntroductionRecurrent aphthous ulcers are common but poorly understood mucosal disorder. Local and systemic conditions, genetic, immunological, and microbial factors may play a role in the pathogenesis of recurrent aphthous ulceration (RAS). Different aetiologies and mechanisms might be involved in the aetiopathogenesis of aphthous ulceration. Cytokines are thought to play an important role and high levels of interleukin (IL)-6, a pro-inflammatory cytokine, have been detected in the circulation of ulcer tissue. The purpose of the present study was to investigate if polymorphisms of IL-6 gene are associated with RAS in a cohort of specific population. MethodologyA total of 37 RAS patients and 18 healthy controls were included in the study. The genotypes of IL-6 gene −174G\\C polymorphisms were determined using polymerase chain reaction and sequencing. ResultsFour SNPs were analyzed, one known mutation which been evaluated as a risk factor for RAS, and three new mutations were investigated. The genotype frequencies of −174G\\C polymorphism showed no statistically significant differences between RAS patients and controls (p\\ 0.629). Polymorphisms of Rs1800795 heterozygous genotype were found in 21.62% of cases, and 33.33% of controls. Homozygous mutant genotype was found in 5.41% of cases and no homozygous mutant genotype was found in control group. The normal alleles were found in 72.97% of cases and 66.67% of control. ConclusionThus, according to our study, IL-6 gene polymorphism is not involved in RAS pathogenesis. Further studies should be done on large sample size to detect any association with pathogenesis. However, an alternative reasoning could point out to a complex interactive effect on IL-6 expression that might exist between any of the detected polymorphisms.

Interaction of Interleukin 7 Receptor (IL7R) and IL6 Gene Polymorphisms with Smoking Associated with Susceptibility to Asthma in Chinese Han Adults

ABSTRACT Background the aim of this study was to investigate the relationship between the risk of asthma and multiple single nucleotide polymorphisms (SNPs) in interleukin 7 receptor (IL7R) and IL6 genes, as well as the gene- environment interactions. Methods This is a hospital- based case- control study. A total of 430 patients with asthma were continuously recruited. Four SNPs within IL7R and IL6 gene were genotyped by PCR based restriction fragment length polymorphism. The Hardy- Weinberg balance of all participants was tested by SNPstats. The best interaction combination of four SNPs in IL7R and IL6 genes and smoking was screened by generalized multifactor dimensionality reduction (GMDR). Logistic regression was used to test the association between four SNPs and asthma, and stratified analysis for rs1800795 gene-smoking interaction, synergy index (SI) was calculated. Results The rs1494558-G and rs1800795-C were associated with an increased risk of asthma, adjusted ORs (95% CI) was 1.81 (1.29–2.42) and 1.75 (1.20–2.28), respectively. GMDR indicated that the test accuracy for two-locus model involving rs1800795 and smoking was 0.5721, and the p = .011, the results providing evidence for rs1800795 gene-smoking interaction. The asthma risk was higher in smokers with GC or CC genotype than the sum of risks in subjects with smoking or GC or CC genotype alone, compared to the never smokers with GG genotype, the OR (95%CI) was 4.97 (3.01–7.24), and the synergy index (SI) was 1.68 (1.08–2.60). Conclusions The rs1494558-G and rs1800795-C alleles, gene- environment interaction between rs1800795 and smoking were all associated with increased asthma risk.

POLYMORPHISM OF INTERLEUKIN-10 (-819) GENE IS NOT ASSOCIATED WITH LIVER DAMAGE AMONG CHRONIC HEPATITIS B PATIENTS

Introduction: Chronic hepatitis B (CHB) is characterized by chronic liver inflammation and hepatocellular damage caused by hepatitis B virus (HBV), leading to fatal liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). Liver damage causes elevated levels of serum alanine aminotransferase (ALT). Previous studies have shown that IL-10 gene polymorphism (-819 C/T) is linked to several diseases, including inflammatory, autoimmune diseases, and cancer. Purpose: To investigate the relationship between IL-10 gene polymorphisms (-819 C/T) and liver damages in chronic hepatitis B patients at Arifin Achmad Regional Hospital, Riau Province. Method: This study was an analytical study with a cross-sectional approach. Liver damages were examined by measuring ALT levels, and IL-10 gene polymorphisms were analyzed using Amplification-Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR). Results: There were 74 subjects included in this study, aged 45.47±13.42 years old, consisting of 43 males (58.1%) and 31 females (41.9%). Of 74 subjects, 35 CHB patients were presented without complication, 26 CHB patients were complicated with cirrhosis, and 13 CHB patients were complicated with hepatoma. The genotype of the IL-10 (-819) gene polymorphism in this study was found as follows: CT genotype in 34 subjects (45.9%), TT genotype in 30 subjects (40.5%), and CC genotype in 10 subjects (13.5%). There was no significant relationship between IL-10 gene polymorphisms (- 819) and liver damage in chronic hepatitis B patients (p&gt; 0.05). Conclusion: IL-10 gene polymorphism (-819) may not contribute to liver damages among CHB patients.

IL-13 gene polymorphisms (-1112 C/T and -1512 A/C) in patients with chronic and aggressive periodontitis: Effects on GCF and outcome of periodontal therapy.

IL-13 is the key cytokine in the regulation of inflammatory with an autoimmune disease and has an anti-inflammatory effect. This study aimed to compare IL-13 (-1112 C/T and -1512 A/C) gene polymorphisms in patients with aggressive periodontitis (AgP), chronic periodontitis (CP), and periodontally healthy group (C) and evaluate the effect of nonsurgical periodontal therapy on gingival crevicular fluid (GCF) IL-13 levels in patients. One hundred thirty patients with AgP, 120 patients with CP, and 70 periodontally healthy subjects were included in this study. Clinical parameters were recorded (plaque and gingival index, probing pocket depth, clinical attachment level), and GCF and blood samples were taken at baseline and 6-week. Nonsurgical periodontal therapy was performed in patients with periodontitis. Gene analyses (IL-13 - 1112C/T (rs1800925) and - 1512 A/C (rs1881457) were performed with real-time polymerase chain reaction (PCR) and cytokine levels were determined by an enzyme-linked immunosorbent assay method. AgP and CP patients showed significant improvement in clinical parameters after periodontal therapy (P < 0.05). According to results, genotype distributions and allele frequencies in IL-13 variants - 1112C/T and - 1512 A/C were found similarly in all groups (P > 0.05). In the AgP group, GCF IL-13 cytokine level is statistically significant and increased in 6 weeks; however, in the CP group, there is no statistically significant difference between baseline and 6 week. In the AgP group, baseline GCF IL-13 cytokine level is lower than those of the CP group and C group (P < 0.05). Within the limits of this study, IL-13 -1112 and -1512 gene polymorphisms have not been associated with AgP and CP, and GCF IL-13 cytokine level is increased after treatment in the AgP group.

Associations of IL13 gene polymorphisms and immune factors with Schistosoma haematobiuminfection in schoolchildren in four schistosomiasis-endemic communities in Ghana.

BackgroundSchistosomiasis remains a major public health issue with over 90% of the prevalence rates recorded in Sub-Saharan Africa. In this study, the relationships between different interleukin gene polymorphisms (IL-13-591A/G, IL-13-1055C/T, IL-13-1258A/G) and Schistosoma haematobium infection levels were evaluated; as well as the host plasma antibodies and cytokine profiles associated with schistosomiasis infection.MethodologyA total of 469 school children aged 6 to 19 years from four schistosomiasis-endemic communities in Ghana were involved. Single urine and stool samples were obtained from each pupil, processed via sedimentation and Kato-Katz, and examined via microscopy for Schistosoma and soil-transmitted helminth (STH) eggs. Next, venous blood samples were drawn from 350 healthy pupils, and used to measure antibody and plasma cytokine levels by ELISA. Single nucleotide polymorphisms in the IL-13 gene were genotyped on 71 selected blood samples using the Mass Array technique.Principal findings and conclusionThe overall prevalence of urinary schistosomiasis was 21.11%. Community-level prevalences were 17.12%, 32.11%, 20.80%, and 15.32% for Asempaneye, Barikumah, Eyan Akotoguah, and Apewosika respectively. Generally, higher S. haematobium infection prevalence and intensity were recorded for participants with genotypes bearing the IL13-1055C allele, the IL13-591A, and the IL13-1258A alleles. Also, higher S. haematobium infection prevalence was observed among participants in the 12-14-year age group with the IL13-1055C, IL13-591A, and IL13-1258A alleles. Interestingly, higher STH prevalence was also observed among participants with the IL13-1055C, IL13-591A, and IL13-1258A alleles. Furthermore, the age-associated trends of measured antibodies and cytokines of S. haematobium-infected school-children depicted a more pro-inflammatory immune profile for pupils aged up to 1l years, and an increasingly anti-inflammatory profile for pupils aged 12 years and above. This work provides insight into the influence of IL-13 gene polymorphisms on S. haematobium, and STH infections, in school-aged children (SAC).

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.

Contributing role of TNF, IL-10, sTNFR1 and TNF gene polymorphisms in disease severity of leptospirosis.

The immune response is hypothesized as an important factor in the disease outcome of leptospirosis. Exaggerated immune response may promote tissue damage that lead to severe disease outcome. In this study TNF, IL-10, sTNFR1 levels were measured among sixty-two hospitalized leptospirosis confirmed patients in Sri Lanka. Thirty-one serum samples from healthy individuals were obtained as controls. PCR–RFLP method was used to identify TNF gene polymorphisms and to determine their association with TNF expression and disease severity in leptospirosis. TNF (p = 0.0022) and IL-10 (p < 0.0001) were found to be significantly elevated in leptospirosis patients, while sTNFR1 (p < 0.0001) was significantly suppressed. TNF was not significantly elevated in patients with complications while the anti-inflammatory cytokine IL-10 was significantly elevated among patients with complications (p = 0.0011) and with mortality (p = 0.0088). The ratio of IL-10 to TNF was higher among patients with complications (p = 0.0008) and in fatal cases (p = 0.0179). No association between TNF gene polymorphisms and TNF expression was detected due to the low frequency of heterozygous and mutated genes present in this study population. Thus the findings of the study show that elevated levels of IL-10 in the acute phase of disease could lead to severe outcomes and a high IL-10/TNF ratio is observed in patients with complications due to leptospirosis.

Interleukin-10-592 polymorphism: impact on relapse and survival after allogeneic hematopoietic stem cell transplantation in children with hematological malignancies

PurposeInterleukin-10 (IL-10) potentially can promote the development of alloimmunity. The aim of this study was to investigate if the IL-10-592 CC genotype in the donor reduces the risk of relapse after hematopoietic stem cell transplantation (HSCT) and if that has an impact on event-free survival (EFS) and overall survival (OS).MethodsA cohort of 211 children with acute lymphoblastic leukemia (n = 99), acute myeloid leukemia (n = 69), myelodysplastic syndrome (n = 31) or chronic myeloid leukemia (n = 12) who underwent hematopoietic stem cell transplantation (HSCT) in a single center and their respective donors were genotyped of IL-10 gene for rs1800872 using TaqMan real-time polymerase chain reaction.ResultsThe IL-10-592 CC genotype was detected in 107 of the 211 donors (50.7%) and in 106 of the 211 patients (50.2%). Genotype AC was found in 95 donors (45.0%) and in 90 patients (42.7%). Nine donors (4.3%) and 15 patients (7.1%) were homozygous for AA. Ultimately, we observed a significantly reduced incidence of relapse rate (RR) in patients who were transplanted from a donor with the IL-10-592 CC genotype (19% versus 43% (AC) versus 49% (AA); P = 0.0007). In addition, a significant increase of EFS (P = 0.004) and OS (P = 0.006) was detected if the IL-10-592 CC genotype is present in the donor. The occurrence of the IL-10-592 CC genotype, in either donors or recipients, had no significant impact on acute and chronic graft-versus-host disease. In addition, the IL-10-592 genotype of the recipients was not relevant for the RR (P = 0.47434), the EFS (P = 0.840), and the OS (P = 0.535).ConclusionThe IL-10-592 CC genotype in the donor was associated with a significant decrease of RR which led to a significant increase of EFS and OS after HSCT. This is the first study to describe an association of the IL-10 gene polymorphism with RR, EFS, and OS after HSCT. Selecting a donor with the IL-10-592 CC genotype could be a useful therapeutic strategy for improving the outcome after allogeneic HSCT.

Association of interleukin-6 (174 G/C) and interleukin-12B (1188 A/C) gene polymorphism with expression and risk of Japanese encephalitis disease in North Indian population

BackgroundJapanese encephalitis is an acute inflammatory disease caused by Japanese encephalitis virus (JEV). In this study we aim to determine the association of IL-6 (174) and IL-12B (1188A/C) gene polymorphisms with JEV susceptibility, disease severity and outcomes in north Indian population. MethodsThis study was performed an equal number of cases and control individuals (125). Gene polymorphism has been analyzed by PCR-RFLP and expression by ELISA. ResultsHomozygous(C/C) genotypes of IL-12B were significantly associated with protection in JE infection (p = 0.008, OR = 0.368) whereas IL-6 was not associated with JEV infection (p = 0.269, OR = 1.245). The C allele of IL-6 was associated with protection in JE disease and G/C genotype was associated with outcomes with recovered individuals. ConclusionIL-12B gene polymorphism leads to increase level of IL-12B in JE patients, which can contribute to JE susceptibility and disease severity. IL-6 polymorphism has not been associated with susceptibility of JE. Overall, this is the first information from northern India shows association of IL-6 and IL-12B polymorphisms with JE disease.

Association of TGF-β1 and IL-10 Gene Polymorphisms with Osteoporosis in a Study of Taiwanese Osteoporotic Patients

Osteoporosis is a rising health threat in the increasingly aging world population. It is a common skeletal disease strongly linked to genetic predisposition. We aim to identify the effects of the anti-inflammatory TGF-β1- and IL-10-specific single-nucleotide polymorphism (SNP) combination on the risk for osteoporosis. We investigated and analyzed the relationships between three TGF-β1 SNPs (−509C/T, +869 T/C and +29T/C), one IL-10 SNP (+1927A/C) and the level of bone mineral density (BMD), as well as the risk of osteoporosis in Taiwanese osteoporotic patients. A total of 217 subjects were recruited, including 88 osteoporotic patients and 129 healthy controls, for SNPs, BMD and clinical characteristics statistical analyses. Females with TGF-β1 SNP (−509 C/C) and IL-10 SNP (+1927 C/C) genotypes showed a great benefit for femoral neck T-scores. However, the combination of TGF-β1 SNP (−509 T/T) and IL-10 SNP (+1927 A/A) genotypes in all subjects showed a significant decrease in total hip BMD T-scores. The TGF-β1 SNP (−509 C/T) genotype in all subjects and TGF-β1 SNP (−509 T/T) and IL-10 SNP (+1927 A/C) genotypes in males showed positive effects on body height. The combination of the many SNPs in the anti-inflammatory TGF-β1 and IL-10 genes may be cooperatively involved in the development of osteoporosis. Our data suggested that the specific SNP combination of TGF-β1 (−509) and IL-10 (+1927) may act as a predictive factor for postmenopausal osteoporosis in Taiwanese women.

IL17F: A Possible Risk Marker for Spondyloarthritis in HLA-B*27 Negative Brazilian Patients.

HLA-B*27 is an important marker for spondyloarthritis (SpA), however, many SpA patients are HLA-B*27 negative. Thus, the aim of this study was to investigate the influence of IL17, TNF and VDR gene polymorphisms in SpA patients who were HLA-B*27 negative. This case-control study was conducted in 158 patients [102 patients with ankylosing spondylitis (AS) and 56 with psoriatic arthritis (PsA)] and 184 controls. HLA-B*27 genotyping was performed using PCR-SSP and IL17A (rs2275913), IL17F (rs763780), TNF-308 (rs1800629), TNF-238 (rs361525), FokI C>T (rs2228570), TaqI C>T (rs731236), ApaI A>C (rs7975232), and BsmI C>T (rs1544410) using PCR-RFLP. Statistical analyses were performed by Chi-square and logistic regression using OpenEpi and SNPStats software. The IL17F C allele frequency was higher in patients with SpA, AS and PsA compared to controls. The IL17F T/C genotype frequency was higher in SpA patients in an overdominant inheritance model and when men and women were separately analyzed. IL17A_IL17F AC haplotype was significantly associated to the risk for SpA patients. As for VDR, the ApaI a/a was a potential risk factor for SpA in men. In conclusion, IL17F C variant contributed to the risk of SpA in Brazilian patients who were HLA-B*27 negative and could be a potential marker for SpA.

The impact of IL-10 and CYP3A5 gene polymorphisms on dose-adjusted trough blood tacrolimus concentrations in early post-renal transplant recipients.

The strong inter-individual pharmacokinetic variability and the narrow therapeutic window of tacrolimus (TAC) have hampered the clinical application. Gene polymorphisms play an important role in TAC pharmacokinetics. Here, we investigate the influence of genotypes of IL-10, CYP3A5, CYP2C8, and ABCB1 on dose-adjusted trough blood concentrations (the C0/D ratio) of TAC to reveal unclear genetic factors that may affect TAC dose requirements for renal transplant recipients. Genetic polymorphisms of IL-10, CYP3A5, CYP2C8, and ABCB1 in 188 renal transplant recipients were determined using Kompetitive Allele Specific PCR (KASP). Statistical analysis was applied to examine the effect of genetic variation on the TAC C0/D at 5, 10, 15, and 30days after transplantation. Recipients carrying the IL-10 -819C > T TT genotype showed a significantly higher TAC C0/D than those with the TC/CC genotype (p < 0.05). Additionally, the TAC C0/D values of recipients with the capacity for low IL-10 activity (-819 TT) engrafted with CYP3A5 non-expressers were higher compared to the intermediate/high activity of IL-10 -819C > T TC or CC carrying CYP3A5 expressers, and the difference was statistically significant at different time points (p < 0.05). Genetic polymorphisms of IL-10 -819C > T and CYP3A5 6986A > G influence the TAC C0/D, which may contribute to variation in TAC dose requirements during the early post-transplantation period. Detecting IL-10 -819C > T and CYP3A5 6986A > G polymorphisms may allow determination of individualized tacrolimus dosage regimens for renal transplant recipients during the early post-transplantation period.

Associations between IL-1RN variable number of tandem repeat, IL-1β (−511) and IL-1β (+3954) gene polymorphisms and urolithiasis in Uighur children of China

ObjectiveInterleukin-1 (IL-1) is a pro-inflammatory cytokine which may be related to urolithiasis. Genetic polymorphisms of the interleukin-1beta (IL-1β) have been proposed as markers for urolithiasis in some areas. Due to the high incidence of urolithiasis in Uighur children (Xinjiang, China) and existence of ethnic difference, our aim is to explore the potential of IL-1 gene polymorphisms and urolithiasis among these children. MethodsGenomic DNA extracted from peripheral blood of 115 patients and 98 controls were used for genotype polymorphisms analyses. IL-1 receptor antagonist (IL-1RN) gene variable number of tandem repeat (VNTR) gene polymorphisms were analyzed by PCR method. PCR-based restriction analysis was done for the IL-1β (−511) and IL-1β (+3954) gene polymorphisms by endonucleases Ava I and Taq I, respectively. The genotype distribution, allele frequencies, carriage rate, and haplotype frequencies were statistically analyzed. ResultsNo significant differences were observed in genotypic frequencies between pediatric urolithiasis patients and control group for IL-1RN gene (χ2=1.906, p=0.605), IL-1β (−511) gene (χ2=0.105, p=0.949), or IL-1β (+3954) gene (χ2=3.635, p=0.169). There were yet no significant differences of the allele frequencies of IL-1RN VNTR gene (p=0.779), IL-1β (−511) gene (p=0.941), and IL-1β (+3954) gene (p=0.418) in the case and control groups, as well as the carriage rate and haplotype of them (all p>0.05). ConclusionsThe associations between IL-1RN VNTR, IL-1β (−511) and IL-1β (+3954) genes polymorphisms and urolithiasis were not significant in Uighur children. The results need to be confirmed in studies with larger population sample size, as well as in other ethnic groups.

Cytokine gene polymorphisms in lymphoma: Thesis Abstract

Thesis Abstract Several cytokines are known to be involved in the pathogenesis of non-Hodgkin Lymphomas (NHL). Given the importance of understanding the genetic predisposition involved in the pathogenesis of NHL, this work was designed to study the impact of IL-10 (-1082 G/A; rs1800896 and -819 C/T; rs1800871), IL-6 (-174 G/C; rs1800795) and CD38 (184C/G; rs6449182) gene polymorphisms on the susceptibility of Egyptians to NHL. Both loci of IL10 were genotyped using polymerase chain reaction- sequence-specific primers (PCR-SSP), IL6 rs1800795 G/C was genotyped using mutagenically separated PCR (MS-PCR) and restriction fragment length polymorphism-PCR (RFLP-PCR) was used to genotype CD38 (rs6449182 C/G) in 100 Egyptian patients and 119 controls. Plasma levels of IL-6 and IL-10 were measured using enzyme-linked immunosorbent assay (ELISA). An insignificant change in IL-10 (rs1800896 and rs1800871) genotypes were recorded. GT haplotype was significantly elevated.

Association of IL-10 (\u2212\u20091082 A/G) and IL-6 (\u2212\u2009174\u2009G/C) gene polymorphism with type 2 diabetes mellitus in Ethiopia population

BackgroundInterleukin (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.MethodsA 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.ResultParticipants 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)).ConclusionOur 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.

Association between IL-18 and IL-6 gene polymorphisms and the risk of T1D in Egyptian children.

To test the involvement between IL-18 and IL-6 genetic polymorphisms and susceptibility to Type 1 diabetes (T1D). Single nucleotide polymorphisms (SNPs) at positions -607A/C and - 137G/C in IL-18 promoter region were examined by sequence specific primers-polymerase chain reaction (SSP-PCR) and position -174G/C in promoter region of IL-6 gene which analyzed by Mutagenically Separated PCR (MS-PCR) in 104 T1D participants and 114 controls. IL-18 -137GC and -137CC genotypes and -137C allele were significantly decreased in T1D subjects (P < 0.05), while -137GG genotype was insignificantly increased as compared to controls. A significant decrease was detected in haplotype -137C/-607C frequency in T1D participants compared with controls (OR = 0.04, P < 0.001). There was significant association between IL-18 -607 of (CC, AC and AA genotypes) in age at diagnosis, glycated hemoglobin (HbA1c) and higher body mass index (BMI) (P < 0.05). This study demonstrated that IL-18 gene promoter polymorphisms might be associated with susceptibility to T1D in Egyptian children. Individuals carrying CC genotype at position -137 of IL-18 promoter may be at a low risk of T1D progression. Additionally, the susceptible combination of IL-18 and IL-6 cytokine genes associated with T1D highlight their risk toward the disease. The online version contains supplementary material available at 10.1007/s40200-021-00763-w.