Investigation on the association between inerleukin-10 -592C/A, 819C/T and -1082A/G gene polymorphisms and development of diabetic nephrophathy

We conducted a case-control study to investigate the association between interleukin (IL)-10-592C/A, -819C/T and -1082A/G polymorphisms and susceptibility to diabetic nephropathy. A hospital-based case-control study was taken in our study. A total of 172 patients with proven type 2 diabetes mellitus and 344 controls were recruited from the First Affiliated Hospital of Xinxiang Medical University between March 2012 and October 2014. Genotyping of IL-10 -592C/A, -819C/T and -1082A/G polymorphisms was done by done by PCR-RFLP methods. By the χ² test, the distributions of the GG, GA and AA genotypes in IL-10 -1082A/G were significantly different between patients with diabetic nephropathy and control subjects (χ² = 8.09, P = 0.02). By conditional logistic regression analysis, we found that the AA genotype of IL-10 -1082A/G was associated with an elevated risk of diabetic nephropathy compared to the GG genotype in codominant model, and the adjusted OR (95% CI) was 2.38 (1.23-4.57). In dominant model, the GA+AA genotype was associated with a significantly increased risk of diabetic nephropathy compared to the GG genotype in dominant model (OR = 1.47, 95% CI = 1.05-2.16). In recessive model, the AA genotype could influence the susceptibility to diabetic nephropathy when compared with the GG+GA in recessive model (OR = 2.08, 95% CI = 1.12-3.85). In conclusion, we suggested that IL-10 -1082A/G gene polymorphism was correlated with development of diabetic nephropathy, but no association was observed between IL-10 -819T/C and -592A/C and risk of diabetic nephropathy.     

Interleukin-10 -1082A/G polymorphism is associated with the development of acute pancreatitis in a Chinese population

We conducted a case-control study to investigate the association between IL-10 gene polymorphism (-1082A/G, -819T/C, and -592A/C) and risk of acute pancreatitis in a Chinese population. A total of 240 patients with proven acute pancreatitis and 240 control subjects were collected between May 2012 and January 2015. Genotyping of the IL-10-1082A/G, -819T/C, and -592A/C gene polymorphisms was conducted by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. By univariate logistic regression analysis, patients with acute pancreatitis were more likely to have higher BMI (OR=2.12, 95% CI=1.45-3.12; P<0.001) and have a habit of alcohol drinking (OR=2.01, 95% CI=1.37-2.95; P<0.001). There were significant differences in the genotype distributions of IL-10-1082A/G between patients with acute pancreatitis and control subjects (χ²=9.97, P=0.007). By multiple logistic regression analysis, we found that individuals with the GG genotype of IL-10-1082A/G were associated with an increased risk of acute pancreatitis when compared with the AA genotype (OR=2.32, 95% CI=1.20-4.59; P=0.007). In dominant and recessive models, the IL-10-1082A/G gene polymorphism was significantly correlated with an elevated risk of acute pancreatitis, and the adjusted Ors (95% CI) were 1.50 (1.03-2.20) and 1.99 (1.06-3.79), respectively. However, no significant different was found between IL-10-819T/C and -592A/C gene polymorphisms and susceptibility to acute pancreatitis. In conclusion, we suggest that IL-10-1082A/G gene polymorphisms contribute to the development of acute pancreatitis in codominant, dominant and recessive models.     

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.     

Association between Interleukin-10 gene polymorphisms and risk of early-onset preeclampsia

We conducted a case-control study to investigate the role of IL-10 -1082A/G (rs1800896), -819T/C (rs1800871), and -592A/C (rs1800872) polymorphisms in the development of early-onset preeclampsia. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay was applied to assess the polymorphisms of IL-10 -1082A/G (rs1800896), -819T/C (rs1800871), and -592A/C (rs1800872). The genotype distributions of IL-10 -1082A/G (rs1800896), -819T/C (rs1800871), and -592A/C (rs1800872) confirmed with HWE in the controls, and the P value for HWE was 0.41, 0.38 and 0.26, respectively. The results of the multivariate logistic regression analysis revealed that the association of individuals expressing the CC genotype and AC+CC of IL-10 -592A/C (rs1800872) with a significantly increased risk of early-onset preeclampsia in co-dominant and dominant models, compared to the AA genotype; the OR (95% CI) for these individuals was determined to be 2.09 (1.12-3.90) and 1.66 (1.03-2.71), respectively. In the recessive model, we found that CC genotype of IL-10 -592A/C (rs1800872) was associated with the increased risk of early-onset preeclampsia when compared with AA+AC genotype (OR = 1.67; 95% CI = 1.01-2.92). In conclusion, our study has indicated that IL-10 -592A/C (rs1800872) polymorphism was associated with an increased risk of early-onset preeclampsia in a Chinese population.     

Associations between interleukin-10 polymorphisms and susceptibility to psoriasis: a meta-analysis

Objective

The aim of this study was to determine whether three specific interleukin-10 (IL-10) polymorphisms confer susceptibility to psoriasis.

Methods

A meta-analysis was conducted on the associations between the IL-10-1082 G/A, -592 C/A polymorphisms and haplotypes of the IL-10-1082 G/A, -592 C/A, -819 C/T polymorphisms and psoriasis.

Results

A total of eight studies involving 1,018 psoriasis patients and 1,186 controls were considered in the meta-analysis. No association was found between psoriasis and the IL-10-1082 G allele in all study subjects [odds ratio (OR)?=?1.098, 95?% confidence interval (CI)?=?0.923?1.306, p?=?0.291] or between this allele and psoriasis in Europeans (OR?=?0.990, 95?% CI?=?0.809?1.214, p?=?0.925), but a significant association was found in Asians (OR?=?1.785, 95?% CI?=?1.144?2.76, p?=?0.011). Three polymorphisms at the promoter region of IL-10 (-1082 G/A, -819 C/T, -592 C/A) are known to be in complete linkage disequilibrium, but no association was found between the haplotype and psoriasis.

Conclusions

This meta-analysis shows that the IL-10-1082 G/A polymorphism confers susceptibility to psoriasis in Asians, and suggests that the IL-10 promoter -1082 polymorphism has an ethnicity-specific effect.     

Meta-Analysis of Associations Between Interleukin-10 Polymorphisms and Susceptibility to Vasculitis

Objective: This study determined whether interleukin-10 (IL-10) polymorphisms are associated with susceptibility to vasculitis.

Methods: A meta-analysis was conducted of the associations between the IL-10 -1082 G/A, -819 C/T, and -592 C/A polymorphisms and the haplotype of the IL-10-1082 G/A, -819 C/T, -592 C/A polymorphisms and vasculitis.

Results: A total of 21 comparative studies involving 4121 patients and 5504 controls were considered in the meta-analysis. Meta-analysis revealed no association between the IL-10-1082 G allele and vasculitis in all study subjects (OR?=?0.927, 95% CI?=?0.780–1.102, p?=?0.389). However, disease-specific meta-analysis showed an association between Wegener’s granulomatosis (WG) and the IL-10-1082 G allele (OR?=?0.729, 95% CI?=?0.547–0.971, p?=?0.031). Meta-analysis revealed an association between vasculitis and the IL-10-819 C allele (OR?=?0.804, 95% CI?=?0.706–0.916, p?=?0.001) in all study subjects and Behcet’s disease (BD) (OR?=?0.724, 95% CI?=?0.679–0.781, p?<?1.0?×?10^?9). Meta-analysis of the IL-10-592 C allele showed an association with vasculitis in all study subjects (OR?=?0.805, 95% CI?=?0.619–0.938, p?=?0.005) and BD (OR?=?0.718, 95% CI?=?0.661–0.781, p?<?1.0?×?10^?9). Meta-analysis of the IL-10 haplotype revealed an association between the GCC haplotype and vasculitis in Europeans (OR?=?1.239, 95% CI?=?1.105–1.513, p?=?0.035).

Conclusions: This meta-analysis showed that IL-10 polymorphisms are associated with vasculitis susceptibility, especially in WG and BD.     

Association between interleukin-10 -1082A/G, -819C/T and -592C/A polymorphisms with deep venous thrombosis

Background

Deep venous thrombosis (DVT) and inflammation are two closely related entities. The objective of this study was to evaluate a possible association between interleukin-10 (IL-10) -1082A/G, -819C/T and -592C/A polymorphisms with DVT.

Methods

A case-control study was carried out in 660 patients with DVT and 660 age- and gender-matched healthy controls. Polymerase chain reaction restriction fragment length polymorphism (PCR–RFLP) assay was applied to identify the polymorphisms mentioned.

Results

Patients with DVT had a significantly lower frequency of IL-10 -1082GG genotype [odds ratio (OR) = 0.59, 95% confidence interval (CI) = 0.39, 0.89; P = 0.01] than healthy controls. When stratifying by family history of DVT, it was found that patients with positive family history of DVT had a significantly lower frequency of IL-10 -1082GG genotype (OR = 0.13, 95% CI = 0.02, 0.95; P = 0.04). When stratifying by smoking status, presence of varicose veins, type 2 diabetes mellitus and any hormone administration before, no significant differences were found in any groups.

Conclusions

This study provides evidence that IL-10 -1082A/G polymorphism associated with risk of DVT. However, no association of the IL-10 -592C/A or -819C/T polymorphism with DVT risk was found. Additional well-designed large studies were required for the validation of our results.     

Association of IL10 promoter polymorphisms with idiopathic achalasia

Idiopathic achalasia is an esophageal motor disorder of unknown etiology. A wealth of evidence supports the concept that achalasia is an immune-mediated disease. According to this evidence, achalasia has been significantly associated with specific alleles of the human leukocyte antigen class II, PTPN22 and IL23R. Several studies have demonstrated association of the IL10 gene with different inflammatory disorders. Our aim was to evaluate the role of functional IL10 promoter polymorphisms in susceptibility to idiopathic achalasia. A case-control study was performed with the -1082, -819, and -592 IL10 promoter polymorphisms in 282 patients and 529 controls and in an independent replication set of 75 patients and 575 controls. The GCC haplotype of the IL10 promoter was reported to be associated with a lower risk of achalasia in the discovery sample (odds ratio [OR] = 0.79, 95% confidence interval [CI] = 0.64-0.98, p = 0.029). This association was validated in a replication set (OR = 0.69, 95% CI = 0.48-1.00, p = 0.04). In the combined analysis no heterogeneity was observed between the 2 sample sets and the GCC haplotype was significantly associated with the disease (OR(MH) = 0.76, 95% CI = 0.63-0.91, p = 0.003). Our results provide the first evidence for an association between IL10 promoter polymorphisms and idiopathic achalasia, suggesting that the interleukin-10 cytokine may contribute to the pathogenesis of this disease.     

Association of Interleukin 10 Gene Polymorphisms with Autoimmune Thyroid Disease: Meta‐Analysis

The aim of this study was to perform a meta‐analysis of eligible studies and to derive a precise estimate of the association between interleukin 10 (IL10) polymorphisms and susceptibility to autoimmune thyroid disease (AITD). Meta‐analyses were conducted on the associations between AITD and the ‐1082 G/A (rs1800896), ‐819 C/T (rs1800871) and ‐592 C/A (rs1800872) polymorphisms in IL10, and the haplotype of these polymorphisms and AITD. A total of 2903 AITD patients and 3060 controls in 10 eligible studies were included in the meta‐analysis. This meta‐analysis showed significant associations between IL10 at the ‐1082 G allele and overall AITD (OR: 1.44, 95% CI 1.13–1.82, P = 0.003), but no association between the IL10 ‐592 C allele and the ‐819 C allele and AITD. Subgroup studies demonstrated significant associations between the ‐1082 G allele and susceptibility to Graves’ disease. Ethnicity‐specific meta‐analysis revealed significant associations between the ‐1082 G allele and AITD susceptibility in Asian populations; however, in Middle Eastern populations, no association was evident. Meta‐analysis of the IL10 haplotype revealed an association between the ATA haplotype and AITD (OR: 1.17, 95% CI 1.00–1.36, P = 0.04). Meta‐analysis demonstrates that the IL10 polymorphisms are associated with susceptibility to AITD.     

Role of IL-10 gene polymorphisms on the susceptibility for esophageal cancer and its association with environmental factors

We conducted a hospital-based case-control study to investigate the association of three common SNPs (-1082G/A rs1800896, -819T/C rs1800871, and -592A/C rs1800872) of IL-10 gene polymorphisms with the susceptibility to esophageal cancer in a Chinese population. 246 patients with pathologically proven esophageal cancer and 492 healthy control subjects were collected in our study. Genotyping of IL-10-1082G/A rs1800896, -819T/C rs1800871, and -592A/C rs1800872 was performed using the Sequenom MassARRAY platform (Sequenom; San Diego, CA). Unconditional logistic regression analyses showed that subjects carrying the AA genotype and GA+AA genotype of IL-10-1082G/A rs1800896 were associated with an increased risk of esophageal cancer, and the adjusted ORs (95% CI) were 2.19 (1.31-3.64) and 1.44 (1.05-1.99), respectively. However, we did not find significant association of IL-10-819T/C rs1800871 and -592A/C rs1800872 with the development of esophageal cancer. By stratification analysis, we found that IL-10-1082G/A rs1800896 polymorphism has no significant association with smoking, drinking and family history of cancer in the first relatives in esophageal cancer risk (P>0.05). In conclusion, IL-10-1082G/A rs1800896 genetic variation may be employed as candidate biomarkers for the prediction of susceptibility in esophageal cancer.     

白细胞介素10基因启动子区多态性与乙型肝炎病毒感染预后的关联研究

目的探讨中国汉族人白细胞介素10基因(interleukin10gene,IL10)启动子区单核苷酸多态性与乙型肝炎病毒(hepatitisBvirus,HBV)感染、转归的关联。方法采用聚合酶链反应-限制性片段长度多态性分析方法,检测231例HBV感染者,165例HBV感染康复者和135名正常对照者IL10基因启动子-1082G/A、-819T/C、-592A/C位点基因型。结果IL10基因启动子-1082G/A、-819T/C、-592A/C位点基因型和等位基因在HBV感染组、HBV感染康复组和正常对照组之间的分布频率比较差异无统计学意义(P>0.05),在血清HBV-DNA<1×103拷贝/mL的HBV感染者组和HBV-DNA≥1×103拷贝/mL组之间的分布频率比较差异亦无统计学意义(P>0.05);但IL10基因启动子-819T/C和-592A/C位点基因型和等位基因在HBV无症状携带组和慢性乙型肝炎组之间的分布差异有统计学意义(P<0.05),-819T/C位点TT型和-592A/C位点AA型在慢性乙型肝炎组的频率明显较高。结论汉族人IL10基因启动子多态性可能与人群对HBV易感性及感染后的病毒血症水平无显著相关性;但IL10启动子-819T/C和-592A/C位点基因多态性与HBV感染后的肝脏炎症反应有关。     

Haplotypes of the IL10 Gene as Potential Protection Factors in Leprosy Patients

Leprosy is an infectious disease caused by Mycobacterium leprae characterized by dermatoneurological signs and symptoms that has a large number of new cases worldwide. Several studies have associated interleukin 10 with susceptibility/resistance to several diseases. We investigated haplotypes formed by three single nucleotide polymorphisms (SNPs) located in the IL10 gene (A-1082G, C-819T, and C-592A) in order to better understand the susceptibility to and severity of leprosy in an admixed northern Brazil population, taking into account estimates of interethnic admixture. We observed the genotypes ACC/ACC (P = 0.021, odds ratio [OR] [95% confidence interval (CI)] = 0.290 [0.085 to 0823]) and ACC/GCC (P = 0.003, OR [95% CI] = 0.220 [0.504 to 0.040]) presenting significant results for protection against leprosy development, framed in the profiles of low and medium interleukin production, respectively. Therefore, we suggest that genotypes A-1082G, C-819T, and C-592A formed by interleukin-10 polymorphisms are closely related to protection of the leprosy development in an admixed northern Brazil population, in particular ACC/ACC and ACC/GCC genotypes.     

The association between promoter polymorphism of the interleukin-10 gene and Alzheimer's disease

The importance of the role of inflammation has been suggested in the pathogenesis of Alzheimer's disease (AD). Interleukin-10 (IL-10) is an anti-inflammatory cytokine that may modulate the progression of the disease through the inhibition of the action of pro-inflammatory cytokines. In this study, three polymorphisms in the regulatory region of the IL-10 gene (-1082, -819 and -592) in 95 Chinese AD patients and 117 age-matched healthy Chinese subjects were investigated. We found that among the Chinese population, the A and C alleles at the -592 position are strongly linked to the T and C alleles at the -819 position, respectively. A strong association with AD was found for these two IL-10 polymorphisms, which are in complete linkage disequilibrium (-592C and -819C), and the odds ratio of AD is 4.03 (95% CI 1.23-13.23; p = 0.011). The functional significance of the IL-10 genotype was further supported by the significant association between plasma IL-10 concentrations and genotypes that were found in an independent sample of 160 healthy male volunteers. No interaction effect between the ApoE and IL-10 genotypes is found. Therefore, we concluded that the functional polymorphisms of the IL-10 gene act as a risk factor for AD.     

Association of interferon gamma and interleukin 10 genes with tuberculosis in Hong Kong Chinese

Interferon gamma (IFN-gamma) and interleukin 10 (IL-10) are believed to play opposing roles in host immunity against mycobacterial infection. IFN-gamma activates macrophages, while IL-10 downregulates the expression of T helper type 1 cytokines, MHC class II antigens and costimulatory molecules on macrophages. Associations of IFN-gamma -179 (G/T), +874 (A/T), +875 miscrosatellite CA repeats and +4766 (C/T), and IL-10 -1082 (A/G), -819 (C/T) and -592 (C/A) with tuberculosis (TB) were investigated in 385 HIV-negative patients and 451 controls in a Hong Kong Chinese population. The frequency of a low IFN-gamma-producing +874 A/A genotype was significantly over-represented in the patient group (P<0.001, OR=3.79, 95% CI=1.93-7.45). We identified 10 alleles in the IFN-gamma CA repeats and observed a significant difference in allele frequency distribution between patients and controls (P<0.001). By grouping alleles into 12 and non-12 CA repeats, the non-12/non-12 genotype yielded a similar significant result (P<0.001, OR=4.56, 95% CI=2.21-9.43) as observed in +874 A/A genotype. Weak associations of the IL-10 GCC/- genotype (P=0.04) and the low IFN-gamma-producing A/A genotype (P=0.06) with TB relapse/extrapulmonary cases were found. This study suggests the possible role of interferon gamma in TB susceptibility.     

Association of interleukin-10 promoter polymorphisms with systemic lupus erythematosus

Several lines of evidence suggest interleukin-10 gene (IL-10) is a candidate gene in susceptibility to systemic lupus erythematosus (SLE). We investigated the association of IL-10 promoter single-nucleotide polymorphisms (SNPs) (-3575T/A, -2849G/A, -2763C/A, -1082A/G, -819T/C and -592A/C) and microsatellites (IL10.R, IL10.G) with SLE in 554 Hong Kong Chinese patients and 708 ethnically matched controls. Six haplotypes (hts) were identified from the SNPs. The genotype distribution of the ht1 (T-C-A-T-A), which is associated with low IL-10 production, was different in patients and controls (P=0.009). The homozygous genotype of non-ht1 was significantly increased in patients (P=0.009, odds ratio (OR)=1.80, 95% CI: 1.15-2.82). The frequency of IL10.G4 of IL10.G was also significantly increased in patients (P=0.017, OR=2.53, 95% CI: 1.18-5.40). We found that the homozygous non-ht1 combined with short allele (CA repeat number < or =21) of IL10.G has a dose-dependent effect on SLE susceptibility: non-ht1/non-ht1 with homozygous short allele showed a higher OR (OR=4.11, 95% CI: 1.27-13.2, P=0.018) of association with SLE than the genotype of non-ht1/non-ht1 with heterozygous short/long allele (OR=2.98, 95% CI: 1.26-7.07, P=0.013) and homozygous long allele (OR=1.05, 95% CI: 0.62-1.78, P=0.848). The frequency of non-ht1 was significantly increased in patients with serositis (P<0.0001, OR=2.42, 95% CI: 1.55-3.80). In conclusion, the high expression promoter genotype is associated with SLE in Chinese.     

IL-10 promoter genetic polymorphisms and risk of Kawasaki disease in Taiwan

Kawasaki disease (KD) is the most common cause of pediatric acquired heart disease. KD patients have spontaneously high plasma/serum levels of IL-10 during the acute phase. Therefore, two independent studies were carried out to investigate the association between genetic variants in IL-10 promoter (-1082, -819, and -592) and risk of KD. A total of 134 trios were included for the family-based association study. A significantly preferential transmission of the C allele at loci -819 T > C and -592 A > C for KD cases was observed (P permutation = 0.029 and P permutation = 0.034, respectively). There was a significant increase in the transmission of haplotype CC (p = 0.016) at the above two loci (OR, 1.632; 95% CI, 1.090-2.443; P permutation = 0.019). We also carried out a follow-up case-control study that included 146 KD cases and 315 unrelated healthy children. The haplotype CC (-819, -592) showed an increased risk of KD (but statistically non-significant; OR, 1.332; 95% CI, 0.987-1.797; p = 0.061). In diplotype analysis, a trend was found between number of CC haplotype and risk of KD (but non-significant, p =0.061). In conclusion, CC genotype and CC/CC diplotype at IL-10-819T > C and -592A > C were significantly associated with risk of KD in case-parent trio study, which were replicated partially in our follow-up case-control study.     

Association and interaction of the TNF-alpha gene with other pro- and anti-inflammatory cytokine genes and HLA genes in patients with type 1 diabetes from North India

Type 1 diabetes (T1D) is a multifactorial autoimmune disorder where major histocompatibility complex (MHC) genes and the insulin-linked polymorphic region have been shown to play major roles. We report here an integrated effect of tumor necrosis factor (TNF) alpha with other cytokine genes. The TNF-alpha-308 GA and AA (high secretor) polymorphisms were significantly increased in the patients with T1D (n = 235) [P < 7 x 10(-6), odds ratio (OR) = 3.04, 95% confidence interval (CI) = 1.8-5.3] compared with the controls (n= 128). The variants of interferon-gamma (IFN-gamma) (A(+874)T), interleukin (IL)-6 (G(-174)C), IL-10 (A(-1082)G, T(-819)C, C(-592)A) and transforming growth factor (TGF) beta1 (T(cdn10)C, G(cdn25)C) did not show a significant difference between patients and controls. However, simultaneous presence of TNF-alpha-308 GA+AA along with both high and low secretor genotypes of IFN-gamma (P < 0.003) was significantly increased in patients. Simultaneous presence of TNF-alpha-308 GA + AA along with high secretor genotypes of IL-6 (P < 0.0001, OR = 2.61, 95% CI = 1.5-4.56), IL-10 (P < 0.0001, OR = 4.26, 95% CI = 1.9-10.1) and TGF-beta1 (P < 0.00004, OR = 2.8, 95% CI = 1.6-4.86) was also significantly increased in patients with T1D. Low secretor genotype of TNF-alpha-308 GG along with low secretor genotypes of IFN-gamma (P < 0.001, OR = 0.465, 95% CI = 0.28-0.77), high secretor genotypes of IL-6 (P < 0.000004, OR = 0.76, 95% CI = 0.227-0.621) and TGF-beta1 (P < 0.000006, OR = 0.336, 95% CI = 0.198-0.568) was protective. The TNF-alpha-308 G allele was in linkage disequilibrium (LD) with the human leukocyte antigen (HLA)-B*0801-DRB1*0301 haplotype, while TNF-alpha-308 A allele was in LD with the HLA-B*5001-DRB1*0301 and B*5801-DRB1*0301 haplotypes, suggesting that the effect of TNF-alpha -308 A allele is not because of its being in LD with any HLA alleles, but because of its functional role and its integrated effect with other cytokines.     

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.     

Interleukin-10 gene promoter polymorphisms and their protein production in peritoneal fluid in patients with endometriosis

Although associations of interleukin-10 (IL-10) gene promoter polymorphisms and their protein production with endometriosis risk have been reported, the correlations remain controversial. The objective of this study was to determine IL-10 gene promoter polymorphisms at -1082, -819 and -592 sites and their protein production in peritoneal fluid (PF) in patients with and without endometriosis. IL-10 gene promoter polymorphisms at -1082 site were detected by amplification refractory mutation system (ARMS)-PCR and that at -819 and -592 sites was genotyped by restriction fragment length polymorphism (RFLP)-PCR. Protein levels of IL-10 in PF were measured by enzyme-linked immunosorbent assay (ELISA). There were no significant differences in the genotype and allele frequencies of IL-10 gene promoter polymorphisms at position -1082 between the endometriosis and the control groups. However, the frequency of -819 or -592 C alleles was significantly increased in patients with endometriosis compared with controls. The protein levels of IL-10 in PF were statistically higher in the endometriosis group than in the control group. Moreover, the polymorphisms at -1082, -819 and -592 sites were associated with protein levels of IL-10 in PF in the endometriosis group while in the control group only the polymorphisms at position -1082 correlated with protein levels. Increased frequency of -819 or -592 C allele and increased protein production of IL-10 in PF in patients with endometriosis compared with controls and correlations of polymorphisms at -819 and -592 sites with protein levels of IL-10 in PF in patients with endometriosis may suggest that polymorphisms at -819 and -592 sites and their protein production are associated with endometriosis risk.