Interleukin-10 Gene Promoter Polymorphisms Research Articles

Influence of Vitamin D Status and IL-10 Gene Promoter Polymorphism (rs1800871) on Plasma IL-10 Levels in Apparently Healthy Individuals from Southern India: A Cross-sectional Study

Introduction: Interleukin-10 (IL-10) is a major anti-inflammatory cytokine, which plays an important role in regulating inflammatory responses of the immune system. Changes in IL-10 level and its function can cause an imbalance in immune response, which can be associated with various disease conditions. Aim: To study the influence of vitamin D status and IL-10 gene promoter polymorphism (rs1800871) on circulating IL-10 cytokine levels in apparently healthy South Indian population. Materials and Methods: A cross-sectional study was conducted at the Department of Clinical Pharmacology, JIPMER, Puducherry, India from January 2016 to December 2017. Apparently healthy South Indian volunteers (N=101) of either sex, age more than 18 years, were recruited for the study, after obtaining written informed consent. Serum 25-hydroxy vitamin D and plasma IL-10 levels were measured by using Chemiluminescence and Enzyme Linked Immunosorbent Assay (ELISA), respectively. IL-10 rs1800871 genotyping was performed by Real Time-polymerase Chain Reaction (RT-PCR). Values were expressed as median, Interquartile Range (IQR) and proportions were described as number with percentage. Results: The median serum vitamin D and plasma IL-10 levels observed among the study population were 18.21 ng/ mL IQR, 11.3-23.08 ng/mL) and 9.04pg/mL (IQR, 7.75, 11.34 pg/mL) respectively. The genotype and allele frequencies of rs1800871 were consistent with that of the African, South Asian population of 1000 genome project. Plasma IL-10 levels were not significantly different across genotypes (p-value=0.091), even though the median level among homozygous mutant (TT) volunteers was observed to be less (8.35 pg/mL vs 9.69 pg/mL, 9.83 pg/mL). The correlation between vitamin D and IL-10 levels was observed to be insignificant (p-value=0.143). Conclusion: The present study has reported the rs1800871 genotype frequency, circulating serum vitamin D levels and plasma IL-10 levels in the apparently healthy South Indian population. IL-10 cytokine levels were not significant across the different genotype and vitamin D status groups. No significant correlation was observed between the IL-10 and vitamin D levels among the sample studied.

IL-18 Gene Promoter Polymorphisms are Involved in Periodontal Disease: A Meta-Analysis

Microbial plaque that builds up in the gingival crevice area causes inflammation and leads to periodontal disease. Previous research has shown an association between interleukins with periodontitis. The association between interleukin-18 (IL-18) gene polymorphism and periodontitis risk was studied extensively, but the results are contradictory. The aim of this study is to find the association of two IL-18 promoter variants namely -607 C > A (rs1946518) and -137 G > C (rs187238), and the risk of chronic and aggressive periodontal disease by meta-analysis. The databases of PubMed, Medline, Web of Science, and Google Scholar were all explored to find the appropriate studies. The MetaGenyo software was used to calculate each analysis. Outcomes of the pooled analyses revealed significantly elevated risk for periodontitis for both polymorphisms. There is no significant heterogeneity between studies. No significant publication bias was observed. This meta-analysis provided the evidence of a link between IL-18 gene polymorphism in periodontitis.

Interleukin-10 Gene Promoter Polymorphisms and Susceptibility to Asthma: Systematic Review and Meta-analysis.

Several studies have previously assessed the association betweeninterleukin (IL)-10gene polymorphisms and the risk of asthma, leading to conflicting results. To resolve the incongruent outcomes yielded from different single studies, we conducted the most up-to-date meta-analysis ofthe IL-10gene rs1800896, rs1800871, and rs1800872 single-nucleotide polymorphisms (SNPs) and susceptibility to asthma. A systematic literature search performed until April 2020, and the pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were calculated to determine the association strength. Thirty articles comprising 5678 asthmatic patients and 6079 controls met the inclusion criteria. No significant association was found between rs1800872 SNP and susceptibility to asthma across all genetic models in the overall and subgroup analyses. The rs1800871 SNP had only significant association with a decreased risk of asthma in Europeans (OR 0.66, CI 0.53-0.82, P < 0.001). However, rs1800896 SNP was significantly associated with a decreased risk of asthma by dominant (OR 0.67, CI 0.50-0.90, P < 0.001) and heterozygote (OR 0.66, CI 0.49-0.88, P < 0.001) models in the overall analysis. Subgroup analyses indicated significant association of rs1800896 SNP by dominant (OR 0.45, CI 0.28-0.72, P < 0.001) and heterozygote (OR 0.43, CI 0.26-0.70, P < 0.001) models in the African population. The IL-10 rs1800896 SNP confers protection against the risk of asthma, especially in Africans. Additionally, rs1800871 SNP has a protective role against asthma in Europeans.

The Association between Interleukin-10 Gene Polymorphisms and Hepatitis B Virus: Evidence in Iran

Background and Aim: Hepatitis B virus (HBV) is a human carcinogenesis agent. Interleukin 10 (IL-10) is a key anti-inflammatory cytokine, and single nucleotide polymorphisms in IL-10 gene promoter are correlated with infections caused by HBV. This research intended to assess the prevalence and genotype of HBV as well as the association between the polymorphisms of -819 and -1082 in the IL-10 gene with HBV in individuals with HBV infection in Qom Province, Iran Methods: In this cross-sectional research, 360 individuals with chronic HBV infection and control group were involved between July 2018 and March 2019. HBV diagnosis was evaluated using ELISA and nested PCR assays. To determine polymorphisms in the IL-10 gene promoter in HBV positive and control samples, an allele-specific polymerase chain reaction technique was employed. Results: The constructed phylogenetic trees for the HBsAg gene revealed that all sequences under study belong to genotype D and also, the majority of HBV samples presented similar sequences to the Iranian samples. Genotype frequencies of TT, TC and CC (polymorphism -819) were 82.2%, 11.6% and 6.1% for patients and 85%, 10.5% and 4.4% in control groups, respectively. Also, frequency of genotypes of AA, AG and GG (polymorphism -1082) were 45%, 43.8% and 11.1% for patients and 42.2%, 46.1% and 11.6% in control groups, respectively. Conclusion: Here, we found no association among IL-10 gene polymorphisms in control and HBV-infected groups. However, more studies about the frequency of chronic HBV infection are necessary to be conducted. *Corresponding Author: Mohsen Zargar; Email: zargar@qom-iau.ac.ir Interleukins-10 Gene Polymorphism and Hepatitis B Virus: Evidence in Iran. Arch Med Lab Sci. 2021;7:1-7 (e7). https://doi.org/10.22037/amls.v7.33557

Association of IL-10 gene promoter polymorphisms with susceptibility to pseudoexfoliation syndrome, pseudoexfoliative and primary open-angle glaucoma

BackgroundThe involvement of cytokines in pathogenesis of pseudoexfoliation syndrome and glaucoma has been demonstrated in several studies. The aim of the present study was to explore the association between three promoter polymorphisms −592C/A (rs1800872), − 819C/T (rs1800871) and -1082A/G (rs1800896) of interleukin 10 (IL-10) gene with susceptibility to pseudoexfoliation syndrome (PEX), pseudoexfoliative glaucoma (PEXG), and primary open-angle glaucoma (POAG).MethodsIn this study, 114 PEX, 118 PEXG, 114 POAG patients and 126 healthy individuals from Iranian population were participated. Detailed ophthalmic examinations by an ophthalmologist including slit-lamp bio-microscopic examination, dilated examination of the lens, gonioscopy, and funduscopy were carried out on patients and controls. Genomic DNA was extracted from the blood samples and ARMS–PCR was performed to detect promoter polymorphisms of IL-10.ResultsIn all three SNPs studied, there was a significant difference in the genotype distribution between patients and control subjects. Results revealed that the AA genotype of IL-10 -592C/A SNP is associated with PEX. However, TT genotype of −819C/T and AA genotype of -1082A/G SNP are significantly associated with susceptibility to either PEX or PEXG and POAG disorders. Furthermore, the ACC haplotype containing the IL-10 -1082A allele was associated with PEX (P = 0.02, OR = 5.76, 95% CI = 5.17–24.49), PEXG (P = 0.006, OR = 7.54, 95% CI = 6.62–30.76) and POAG (P = 0.003, OR = 8.11, 95% CI = 7.13–33.15).ConclusionsOur results demonstrated that IL-10 gene promoter polymorphisms are associated with susceptibility to PEX, PEXG and POAG in Iranian population. Considering the fact that IL-10 polymorphisms are associated with various IL-10 expressions, further research is needed to explain its involvement in these disorders and the formation of extracellular fibrillar amyloid deposits in PEX and PEXG.

Interleukin-6 gene polymorhisms and interleukin-6 levels are associated with atherosclerosis in CKD patients.

Inflammation is a major risk factor for atherosclerosis. Genetic polymorphisms in the inflammatory cytokine genes have been associated with atherosclerosis. Because levels of inflammatory cytokines are markedly elevated in patients with chronic kidney disease (CKD), we hypothesized that genotypic variations in the interleukin-6 (IL-6) gene are a cause of systemic inflammatory states and atherosclerosis in South African CKD patients. 120 CKD patients and 40 healthy controls were included. Serum IL-6 and high-sensitivity C-reactive protein (hs-CRP) levels were measured. Functional polymorphisms in the IL-6 genes were genotyped using polymerase chain reaction-sequence specific primer (PCR-SSP) methods. Carotid intima-media thickness (CIMT) and the presence of plaque were assessed by B-mode ultrasonography. Serum IL-6 and hs-CRP levels were increased in patients with CKD compared with healthy controls (p < 0.001). In CKD patients, serum IL-6 above the median value was associated with carotid plaque (OR: 2.11; 95% CI: 1.74-2.57, p=0.004), with excess risk confined to the group with high IL-6 levels. Significant associations were found between the IL-6 gene and atherosclerosis in the CKD group (for G/G genotype: OR=1.21, 95% CI=1.05-1.39, p=0.012; for GG+GC vs. CC: OR=1.14, 95% CI=1.02-1.28, p=0.035). Patients with GG+GC genotype of the IL-6 gene polymorphism had higher levels of IL-6 than those with CC genotype (p=0.029). In South African CKD patients, the IL-6 gene promoter polymorphism is associated with high serum IL-6 levels and atherosclerosis. The relationship between atherosclerosis and -174G/C polymorphism in the IL-6 gene suggests that IL-6 may be a potential pro-inflammatory mediator of atherosclerosis in CKD patients.

Interleukin-10 promoter gene polymorphisms are associated with the first major depressive episode in chronic hepatitis C patients

To investigate the association of IL10 SNPs in chronic hepatitis C (CHC) patients with and without the first major depressive episode (MDE), as well as their association with plasma levels of target cytokines. A hundred and thirty two CHC patients (32 with and 100 without first MDE) and 98 controls were prospectively enrolled in this cross-sectional study. MDE was diagnosed by a psychiatrist, using the Mini International Neuropsychiatric Interview Plus 5.0. IL10 polymorphisms (-1082 G/A, -819C/T and -592C/A IL10 SNPs) were evaluated by Taqman SNP genotyping assay. Plasma concentrations of IL-2, IL-6, IL-10, IFN-γ and TNF-α were determined using the Human Th1/Th2 Cytometric Bead Array kit. The associations were investigated by logistic models. The frequencies of the studied IL10 SNPs did not differ between the CHC patients and controls. The first MDE was positive and independently associated with the IL10-1082*A, IL10-819*T and IL10-592*A (ATA) low producer haplotype (OR = 1.50; 95% CI = 1.11-2.04; P = 0.009) and current alcohol misuse (OR = 4.29; 95% CI = 1.22-15.05; P = 0.02), and inversely associated with increasing age (OR = 0.94; 95% CI = 0.91-0.98; P = 0.006). In addition, plasma level of TNF-α was significantly higher in the carriers than in the non-carriers of the IL10 ATA haplotype in patients with the first MDE. The IL-10 and IL-2 plasma levels were significantly higher in the carriers than in non-carriers of the IL10 GCC high producer haplotype, demonstrating the functionality of the studied IL10 polymorphisms. This is the first study to demonstrate that the IL10 low producer ATA haplotype is associated with the first MDE in patients with CHC.

Impact of Interleukin-6 and Interleukin-10 Gene Polymorphisms on Inhibitor Development in Patients with Moderate and Severe Hemophilia a

Background:An important complication of administration of factor VIII concentrates to treat or prevent bleeding,is the development of autoantibodies that block the activity of the relevant factor (inhibitors). These inhibitory antibodies occur in approximately 25 % of patients with severe hemophilia A. Inhibitors are much less common in patients with mild or moderate disease. Recently, significant progress has been made in our understanding of the mechanisms that lead to inhibitor formation. Polymorphisms of the immune response genes have been suggested to be contributing determinants of the inhibitor risk. Previous immunogenetic studies have shown the implication of human leukocyte antigen (HLA) alleles and some of the cytokine polymorphisms in inhibitors formation such as IL-6 and IL-10.Aim:This study aimed to investigate the associations between interleukin-6 gene promoter polymorphism at position (−174 G/C), interleukin-10 gene promoter polymorphism at position (-1082G/A) and susceptibility of patients with hemophilia A to develop factor VIII inhibitors.Methods and subjects:After medical ethical committee approval, the present study was conducted on 50moderate and severehemophilia A males aged ≤ 18 years who are attending hematology outpatient clinic of Alexandria University Children's Hospital at El-Shatby. The 50 children were undergoing a)Detailed history taking, with special emphasis on: Age of the patient at the time of diagnosis, clotting activity of factor VIII, Age at first exposure to factor VIII, Type and dose of administered factor VIII concentrate. Exposure days (EDs), Age at first surgical intervention, Detection of factor VIII inhibitors b)Laboratory investigations: Identification of genetic variant IL-6 (rs1800795) , IL-10 ( rs1800896 ) using real time PCR.Results:Thirtyone (72.1%) patients had severe hemophilia and 19 (27.9%) had moderate Hemophilia. Eight (16%) of the studied patients were inhibitor positive.As regard interleukin-6 gene promoter polymorphism at position (−174 G/C), the frequency of G allele was greater than C allele in patients who developed inhibitors (χ2= 0.63) with P value = 1.000. regarding interleukin-10 gene promoter polymorphism at position (-1082G/A), the frequency of G allele was greater than A allele in patients who developed inhibitors (χ20.75) with P value = 0.891.There was no statistically significantdifference as regards interleukin-6 polymorphism at position (−174 G/C), interleukin-10 polymorphism at position (-1082G/A) between inhibitor positive and inhibitor negative patients.Conclusion:There was no relation between interleukin-6 polymorphism at position (−174 G/C) , interleukin-10 polymorphism at position (-1082G/A)and the development of factor VIII inhibitors in patients with hemophilia A despite of the high frequency of G allele among inhibitors corresponding to the previous studies done . Further studies are recommended with larger cohort and other SNPs. DisclosuresHassab:Global Blood Therapeutics: Research Funding.

Interleukin 10 gene promoter polymorphisms (rs1800896, rs1800871 and rs1800872) and haplotypes are associated with the activity of systemic lupus erythematosus and IL10 levels in an Iranian population.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with unknown aetiology. According to the role of interleukin 10 (IL10) in SLE pathogenesis, the genetic alterations in its promoter region could be associated with elevated IL10 levels and exacerbated disease. Here, we investigated the association of genotype and haplotype frequencies of three IL10 gene promoter polymorphisms with susceptibility to SLE, IL10 plasma levels and disease activity of patients in an Iranian population. A total of 116 SLE patients and 131 healthy subjects were enrolled. The PCR-RFLP technique was used to detect IL10 promoter genotypes at the positions of -1082 (G/A), -819 (C/T) and -592 (C/A) in association with IL10 plasma levels and SLEDAI scores. The GG genotype of -1082 polymorphism was associated with the increased risk of SLE [OR=2.65, 95% CI (1.21-5.82), p-value=0.046]. The CC genotype in -819 region was associated with SLE susceptibility [OR=3.38, 95% CI (1.26-9.07), p-value=0.034] and C allele was introduced as risk allele [OR=1.86, 95% CI (1.15-3.01), p-value=0.009] in this region. IL10 plasma levels were overexpressed in CC genotype carriers of -592 SNP and decreased in AA genotype carriers of -1082. IL10 was also increased in SLE patients with CGT (-592/-1082/-819) haplotype. The SLEDAI score was higher among CC genotype carriers at the position of -592 and TT genotype carriers at the region of -819. SLEDAI was also elevated among patients with CGC (-592/-1082/-819) and CAC (p=0.011) haplotypes. The present study suggests that the IL10 -819(C/T), -1082(G/A) and -592(C/A) polymorphisms and the haplotypes are associated with SLE susceptibility, increased disease activity and elevated IL10 levels. While this is the first time to report such an association in an Iranian population, further studies are needed to confirm these findings.

Association of IL10 gene promoter polymorphisms with risks of gastric cancer and atrophic gastritis.

ObjectiveTo investigate the association between polymorphisms of the interleukin 10 (IL10) gene and risk of gastric cancer (GC) and atrophic gastritis (AG).MethodsThis study enrolled patients with GC, patients with AG and healthy control subjects. Demographic data were collected and the IL10 gene –1082A/G, –819C/T and –592A/C polymorphisms were genotyped. An enzyme-linked immunosorbent assay was performed to detect Helicobacter pylori infection.ResultsThe study enrolled 556 participants including 208 in the GC group, 116 in the AG group and 232 controls (CON group). In a recessive model of the IL10–819C/T polymorphism, a significantly decreased risk of GC was found compared with AG and non-cancer subjects, respectively (AG→GC: odds ratio OR 0.41; non-cancer→GC: OR 0.57). The CC genotype demonstrated a significantly increased risk of AG compared with CON. Similar significant results were detected in males and H. pylori-negative subgroups. The ACC haplotype was associated with a decreased risk of GC compared with AG. The ATC haplotype was associated with a decreased risk of AG compared with the CON group, but it was associated with an increased risk of GC compared with AG.ConclusionThe IL10 gene promoter –819C/T (rs1800871) polymorphism was associated with the risk of GC and AG in a Chinese population.

Association of interleukin-18 gene promoter polymorphisms with coronary artery disease in northern Iranian population

BackgroundCoronary artery disease (CAD) is the leading cause of disability and mortality in the world. CAD includes a group of cardiovascular diseases such as angina, heart failure and myocardial infarction. Interleukin-18 (IL-18) is a pleiotropic proinflammatory cytokine and an inflammation inducer, which is encoded by the IL-18 gene located on chromosome 11. Different studies have shown the involvement of IL-18 in the pathogenesis of diseases such as atherosclerosis. ObjectiveThis study investigated the association of the IL-18 gene promoter polymorphisms (−137 and −607) with CAD in northern Iranian population. MethodsGenomic DNA was extracted from peripheral blood of 314 patients with CAD and 364 healthy controls by a standard protocol. Sequence-Specific Primer-PCR was used for genotyping. Total RNA was extracted from peripheral blood leukocytes from 80 patients with CAD and 80 healthy individuals using Trizol reagent. Real-time PCR was used to measure the level of IL-18 mRNA in the patients and controls. ResultsAnalysis of genotypes revealed that the frequencies of genotype G/C and allele C in IL-18(−137) polymorphism were significantly lower in patients group than control group (p=0.019 and p=0.028 respectively). No significant difference was found in the IL-18(−607) between the patients and controls. Moreover, the level of IL-18 expression was significantly higher in CAD patients than in controls (p<0.001). ConclusionThe results of the present study suggested a protective effect for genotype G/C of IL-18(−137) in CAD. Moreover, due to an increased expression level of IL-18 in CAD patients, it could be considered as a prognostic and protective factor in this disease.

Interleukin-6 gene polymorphisms and serum erythropoietin and hemoglobin in hemodialysis Iraqi patients.

Chronic kidney disease (CKD) is characterized by elevated levels of pro-inflammatory cytokines. Interleukin-6 (IL-6) is a pleiotropic and pro-inflammatory cytokine involved in different biological activities such as hematopoiesis, inflammation, and acute-phase response. The rate of IL-6 synthesis and degradation is affected by single nucleotide polymorphisms. This study aimed to evaluate the frequencies of 174G/C IL-6 gene promoter polymorphism in Iraqi hemodialysis (HD) patient and to examine the association between the allelic variations and serum erythropoietin (EPO) and hemoglobin (Hb) levels. The frequencies of IL-6 gene polymorphism were studied in 70 chronic renal failure patients on maintenance HD (patients group) and in 20 healthy participants (control group). Genotyping of IL-6 gene was performed by conventional polymerase chain reaction-restriction fragment length polymorphism. The distribution of IL-6 genotypes between groups was similar, and GG genotype is the most frequent followed by CG and CC genotypes. Control group had a nonsignificant difference in serum EPO levels among different IL-6 genotypes, while patients with GG genotype displayed significant elevation in serum EPO with time, followed by CG and CC genotypes. No significant differences in Hb levels were observed in patients and control groups. A significant positive correlation was observed between serum EPO and Hb in control group with different IL-6 genotypes, while a nonsignificant negative correlation was observed in patients group throughout the study. CKD did not significantly alter IL-6 genotypes, and IL-6 gene polymorphism had a significant effect on serum EPO levels and a nonsignificant effect on Hb levels.

Combinations of Interleukin-10 Gene Promoter Polymorphisms with -1082A, -819T, -592A Minor Allele are Associated with Sinonasal Polyposis

Combinations of Interleukin-10 Gene Promoter Polymorphisms with -1082A, -819T, -592A Minor Allele are Associated with Sinonasal Polyposis

Association assessment of Interleukine-10 gene polymorphism and its expression status with susceptibility to coronary artery disease in Iran

BackgroundThe cytokines are potent inflammatory factors that regulate each stage of atherosclerosis leading to the disease development. Interleukin-10 (IL-10) as an anti-inflammatory cytokine can develop atherosclerosis by inhibiting the synthesis of metalloproteinase. Moreover, IL-10 promotes the plaque stability by preserving the extracellular matrix and fibrous cap. AimWe evaluated the association of the two IL-10 promoter gene polymorphisms with susceptibility to coronary artery disease (CAD) in Iranian population. Subjects and methodsWe used the Sequence Specific Primer-Polymerase Chain Reaction method to determine genotypes. We also studied mRNA expression of the IL-10 gene in Iranian CAD patients using quantitative real-time PCR. ResultsThere was a significant association between IL-10(−819) T allele and IL-10(−819) T/T genotype, and CAD (p=0.041 and p=0.042 respectively). There also was a significant association between IL-10(−1082) G allele and IL-10(−1082) G/G genotype, and CAD (p=0.017 and p=0.020 respectively). Genotype T/T of IL-10(−819) polymorphism significantly associated with the two vessel disease type (p=0.017). In addition, there was a significant association between IL-10(−1082) G/G genotype and the three vessel disease type (p=0.009). IL-10 mRNA expression was significantly decreased 3.36-fold in samples with IL-10(−819) polymorphism and 1.98-fold in individuals with IL-10(−1082) polymorphism. ConclusionsOur results suggest that IL-10 gene promoter polymorphisms may influence both coronary artery disease risks and severity in Iranian patients.

Combination of interleukin-10 gene promoter polymorphisms with HLA-DRB1*15 allele is associated with multiple sclerosis

Background & objectives:Multiple sclerosis (MS) is common in some ethnic groups. Interleukin-10 (IL-10) is a potent anti-inflammatory and immunosuppressive cytokine that may be an important regulator in MS disease pathogenesis. IL-10 promoter includes several single nucleotide polymorphisms and the level of IL-10 expression is related to these polymorphisms. Furthermore, loci within the histocompatibility regions are responsible for susceptibility to MS. The aim of this study was to investigate the association of IL-10 gene promoter polymorphisms and HLA-DRB1*15 allele frequencies with MS susceptibility in an Iranian population.Methods:In this study 336 MS patients and 454 healthy controls were included. Genomic DNA was purified from peripheral blood samples by a standard protocol. Genotyping was performed by the sequence-specific primer polymerase chain reaction method.Results:IL-10 −1082 G/G and IL-10 −819 C/C genotypes were more frequent in MS patients than healthy individuals. DRB1* 15 allele showed a higher frequency among MS patients compared to controls.Interpretation & conclusions:The IL-10 and HLA-DRB1*15 polymorphisms were associated with the susceptibility to MS in Iranian patients. Our results suggest that gene-gene interaction of IL-10 polymorphisms and HLA-DRB1*15 alleles may be important factors in the development of MS.

Effect of interleukin-10 gene promoter polymorphisms -1082 G/A and -592 C/A on response to therapy in children and adolescents with chronic hepatitis C virus infection

Background and aimStudying predictors of response to therapy for hepatitis C virus (HCV) infection in children may help avoid the inappropriate use of currently available costly therapy associated with numerous adverse effects. We tested the hypothesis that inheritance of single nucleotide polymorphisms (SNPs) of the interleukin-10 (IL-10) promoter gene might influence response to HCV treatment. Patients and methodsThe impact of SNPs, -1082 G/A and -592 C/A, in the promoter region of IL-10 gene, on response to HCV therapy was assessed in a cohort of 40 children treated with a combination of pegylated interferon (Peg-IFN) α2b and ribavirin. ResultsSustained virological response was achieved in 48.7%. High viral load was associated with non-response to therapy. There was no association between histopathological degree of inflammation or fibrosis and response to therapy. There was no direct statistically significant association between polymorphisms in the IL-10 gene (-1082G/A and -592 C/A) as regards inflammation or response to therapy in children. As for the SNP -592 C/A; there was a statistically significant association with the score of fibrosis (P<0.004), concluding that the A allele was protective from moderate and severe fibrosis. Meanwhile the SNP -1082G/A did not show any association with the fibrosis score. ConclusionWe could not associate response to therapy for HCV with IL-10 polymorphisms -1082 G/A and -592 C/A. For the SNP -592 C/A, the A allele protected from moderate and severe fibrosis.

ACC interleukin-10 gene promoter haplotype as a breast cancer risk factor predictor among Jordanian females.

IntroductionInterleukin-10 (IL-10) is a multifactorial cytokine with a complex biological role in breast cancer. The aims of this study were to investigate any association between IL-10 gene promoter polymorphisms, 1082A>/G, −819T>C, and −592A>C, or haplotypes and breast cancer risk among Jordanian women and to evaluate any association between the most common haplotype with clinicopathological features of breast cancer.Patients and methodsA total of 202 breast cancer patients and 210 age-matched healthy control subjects were genotyped for −1082A/G, −819T/C, and −592A/C single nucleotide polymorphisms in the promoter region of the IL-10 gene by polymerase chain reaction-restriction fragment length polymorphism. Study patients and control subjects were recruited from Prince Hamzah Hospital, Amman, Jordan (2012–2013). Ethical approval and signed consent forms were signed by all participants. DNA was extracted, and polymerase chain reaction fragments were amplified and restriction digested by MnII, MaeIII, and RsaI.ResultsThis study showed no statistically significant difference between −1082A/G, −819T/C, and −592A/C IL-10 genotypes or alleles among breast cancer patients or controls. Four different haplotypes ATA, ACC, GTA, and ACA within the IL-10 promoter gene were determined among both breast cancer and control groups. The most frequent haplotype was ACC among breast cancer patients and controls (41.6% and 40.7%, respectively). No statistical differences in these haplotypes among breast cancer patients or controls were determined. Analysis of the most common ACC haplotype showed statistical difference in positive estrogen receptor (P=0.022), positive progesterone receptor (P=0.004), cancer grade (P=0.0001), and cancer stage (P=0.009) among the ACC haplotype compared to non-ACC haplotype.ConclusionTo our knowledge, this is the first report studying the association of IL-10 haplotype with breast cancer risk events among Jordanian females. The most frequent IL-10 haplotype among Jordanian breast cancer females is ACC haplotype. Patients carrying the ACC haplotype are associated with higher positive estrogen and progesterone receptors and advanced breast cancer grade and stage. These patients also had lower survival rate in the Kaplan–Meier survival plot compared to those with non-ACC haplotype.

Association of interleukin-10 gene promoter polymorphisms with recurrent pregnancy loss: a meta-analysis.

It has been reported single-nucleotide polymorphisms (SNPs) of the IL-10 promoter might be associated with the susceptibility to recurrent pregnancy loss (RPL). Owing to the inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between the IL-10 promoter SNPs and RPL risk. A systematic search of studies on the association of the three SNPs with RPL was conducted in PubMed and Embase. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. Eleven case-control studies on rs1800896, seven studies on rs1800871, and eight studies on rs1800872 were included. A significant association was identified between IL-10 rs1800896 with RPL risk (G versus A: OR = 1.21, 95% CI 1.09-1.35). No evidence of association was found between rs1800871 and RPL when restricted to those studies in Hardy-Weinberg equilibrium in controls (T versus C: OR = 1.25, 95% CI 0.76-2.06). No statistical association was demonstrated between rs1800872 and RPL (C versus A: OR = 1.08, 95% CI 0.83-1.42). IL-10 rs1800896 significantly increases the risk of RPL, while rs1800872 is not correlated with RPL risk. No significant association is demonstrated between rs1800871 and RPL risk but this requires further investigation.

Relationship between IL-10 gene polymorphisms and the risk of non-Hodgkin lymphoma: A meta-analysis

ObjectivesThe purpose of this study was to explore whether interleukin-10 (IL-10) gene promoter polymorphisms and their haplotypes contribute to the incidence of non-Hodgkin lymphoma (NHL). MethodsA meta-analysis was conducted on the associations of the IL-10-3575T/A, -1082 G/A, -819 C/T, -592C/A polymorphisms and the haplotypes with NHL. ResultsA total of 23 studies involving 21,563 NHL patients and 23,837 controls were included in the meta-analysis. Pooled results indicated that IL-10-3575T/A was associated with an increased risk of NHL based on the dominant model (OR: 1.095, 95% CI: 1.020–1.178), similar results were found for -1082A/G in the heterozygous and recessive models (OR: 1.042, 95% CI: 1.012–1.074; and OR: 1.034, 95% CI: 1.011–1.057, respectively). In the ethnic subgroup analysis, -3575T/A had an increased risk of NHL in Caucasians based on the homozygous model (OR: 1.071, 95% CI: 1.001–1.146), and similar results were found for -1082A/G in the heterozygous and recessive models (OR: 1.041, 95% CI: 1.009–1.075; and OR: 1.031, 95% CI: 1.008–1.055, respectively). When stratified by subtypes, -3575T/A and -1082A/G polymorphisms were found significant association with an increased risk of B cell lymphoma, specifically diffuse large B-cell lymphoma (DLBCL). Moreover, -3575T/A was associated with an increased risk of follicular lymphoma (FL) in the homozygous and recessive models. Furthermore, we observed that significantly increased risk of NHL and DLBCL were associated with the A-G-C-C haplotype (IL-10-3575T/A, -1082A/G, -819C/T and -592C/A), and a decreased risk of DLBCL subtype was associated with the T-A-C-C haplotype. ConclusionsIL-10-3575T/A and -1082A/G polymorphisms were associated with altered NHL susceptibility, especially for Caucasians and B cell lymphoma. IL-10 (-3575T/A, -1082A/G, -819C/T and -592C/A) haplotype were associated with NHL and DLBCL subtype.

The -174G/C Interleukin-6 Gene Promoter Polymorphism as a Genetic Marker of Differences in Therapeutic Response to Methotrexate and Leflunomide in Rheumatoid Arthritis.

Objective. To evaluate the association of -174G/C IL-6 polymorphism with failure in therapeutic response to methotrexate (MTX) or leflunomide (LEF). This prospective, observational cohort included 96 Mexican-Mestizo patients with moderate or severe rheumatoid arthritis (RA), initiating MTX or LEF, genotyped for IL-6 -174G/C polymorphism by PCR-RFLP. Therapeutic response was strictly defined: only if patients achieved remission or low disease activity (DAS-28 < 3.2). Results. Patients with MTX or LEF had significant decrement in DAS-28 (p < 0.001); nevertheless, only 14% and 12.5% achieved DAS-28 < 3.2 at 3 and 6 months. After 6 months with any of these drugs the -174G/G genotype carriers (56%) had higher risk of therapeutic failure compared with GC (RR: 1.19, 95% CI: 1.07–1.56). By analyzing each drug separately, after 6 months with LEF, GG genotype confers higher risk of therapeutic failure than GC (RR = 1.56; 95% CI = 1.05–2.3; p = 0.003), or CC (RR = 1.83; 95% CI = 1.07–3.14; p = 0.001). This risk was also observed in the dominant model (RR = 1.33; 95% CI = 1.03–1.72; p = 0.02). Instead, in patients receiving MTX no genotype was predictor of therapeutic failure. We concluded that IL-6 -174G/G genotype confers higher risk of failure in therapeutic response to LEF in Mexicans and if confirmed in other populations this can be used as promissory genetic marker to differentiate risk of therapeutic failure to LEF.