Interleukin-10 gene promoter polymorphisms and the risk of nasopharyngeal carcinoma

Genetic factors are known to be important in the development of nasopharyngeal carcinoma (NPC). Interleukin-10 (IL-10) is an immunosuppressive cytokine which may facilitate development of cancer by supporting tumor escape from the immune response. Interindividual variations in IL-10 production were genetically contributed to polymorphisms within IL-10 promoter region. The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) at positions -1082 (A/G), -819 (T/C) and -592 (A/C) in the IL-10 gene promoter were involved in predisposing an individual to NPC. One hundred and ninety-eight patients with NPC and 210 age- and sex-matched controls, genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism. There were significantly differences in the genotype and allele distribution of -1082 A/G polymorphism of the IL-10 gene among cases and controls. The -1082 AG and GG genotypes were associated with a significantly increased risk of NPC as compared with the -1082 AA genotypes. Haplotype analysis showed that the homozygosity of the GCC haplotype (defined by SNPs at positions -1082, -819 and -592) of IL-10 gene conveys the highest risk for NPC compared with the homozygosity for the ATA haplotype. This study shows for the first time an association between IL-10 gene promoter -1082 A/G polymorphism and its haplotype may contribute to genetic susceptibility to NPC in a Chinese population.     

白细胞介素-10 基因启动子多态性与慢性阻塞性肺疾病易感性的关系

目的　探讨中国汉族人白细胞介素 - 10基因启动子单核苷酸多态性及其与慢性阻塞性肺疾病易感性之间的关系。　方法　应用聚合酶链反应 -限制性片段长度多态性分析方法 ,检测 94名健康吸烟者和 88例吸烟慢性阻塞性肺疾病 (chronic obstructive pulmonary disease,COPD)患者白细胞介素 - 10(interleukin- 10 ,IL- 10 )基因启动子 - 10 82 G/ A、- 819C/ T、- 5 92 C/ A单核苷酸多态性位点基因型。　结果共发现 11种启动子基因型 ,以 AA·TT·AA、AA·TC· AC、AA· TC· AA基因型多见 ;通过对 11种启动子基因型进行分析 ,新发现 ATC、ACA两种单倍型 ;健康吸烟者和吸烟 COPD患者 IL- 10基因启动子- 10 82 G/ A、- 5 92 C/ A位点基因型分布频率差异无显著性 ,- 819C/ T多态性位点与中国汉族人 COPD易感性有关 ;中国汉族人 IL- 10基因启动子等位基因频率与日本人相似 ,与白种人之间差异存在显著性。　结论　中国汉族人 COPD易感性与 IL- 10基因启动子 - 819C/ T位点多态性有关 ;中国汉族人 IL- 10基因启动子至少存在 ATA、ACC、GCC、ATC、ACA5种单倍型。     

Interleukin-10 gene promoter region polymorphism is associated with eosinophil count and circulating Immunoglobulin E in adult asthma

BACKGROUND: IL-10 has several functional effects relevant to asthma. It can modulate IgE production and induce apoptosis in eosinophils. Polymorphisms of IL-10 gene have been shown to affect IL-10 production. OBJECTIVE: To establish whether IL-10 polymorphisms are associated with asthma and phenotype-related characteristics. METHODS: The frequency of three single base exchange polymorphisms (at positions - 1082, - 819 and - 592) and corresponding haplotypes of the IL-10 gene were analysed in 245 adult asthmatic subjects and 405 controls using PCR and restriction fragment length polymorphism (RFLP). The data were assessed for correlations with the eosinophil count, serum IgE and lung function. RESULTS: The IL-10 haplotype frequencies were similar in asthmatics and controls. Eosinophil count median was 2.0- to 3.2-fold higher among asthmatics with rare ATA/ATA genotype than in asthmatics with other genotypes. No such difference was seen in the control group. When analysed by IL-10 haplotype carrier state and gender, male asthmatics with ATA haplotype had 2.8-fold higher serum IgE than those without ATA. A converse association was found in male controls with ATA haplotype, who had 1.9-fold lower serum IgE than their ATA-negative counterparts. The high IL-10-producing GCC haplotype was associated with impaired lung function in smoking male controls while in asthmatics no clear effect on lung function was found with any of the haplotypes studied. CONCLUSION: These results suggest that the eosinophil counts and serum IgE are differently regulated by IL-10 genotype in asthmatic and in normal subjects. However, IL-10 polymorphism is not related to susceptibility in asthma.     

Genetic association between interleukin-10 gene promoter region polymorphisms and type 1 diabetes age-at-onset

This study investigated whether interleukin-10 (IL-10) gene promoter region polymorphisms are associated with susceptibility to or clinical presentation of type 1 diabetes. The frequency of -1082G/A, -819C/T, and -592C/A polymorphisms was analyzed in 128 Japanese patients with type 1 diabetes and in 107 healthy control subjects in a case-controlled study. The allelic and haplotypic frequencies of the IL-10 gene promoter region polymorphisms were similar in patients with type 1 diabetes and in control subjects. However, the -819T and -592A allele were associated with adult-onset (>18 years) of the disease (p = 0.037). Furthermore, the frequency of ATA haplotype was increased in adult-onset patients than that in early-onset patients (< or =18 years; p = 0.037). Among the genotypes comprising ATA haplotype, the frequency of ATA/ATA was significantly higher in adult-onset patients than in early-onset patients (p = 0.004). These results suggest that the IL-10 gene promoter polymorphisms are associated with the age-at-onset in Japanese patients with type 1 diabetes.     

Ethnic variations of IL-10 polymorphisms in a Sami and Norwegian population

Interleukin-10 (IL-10) production is genetically determined and influenced by different polymorphisms in the promoter region of IL-10. These polymorphisms may contribute to the risk and clinical outcome of various infectious and immunological-related diseases. The Samis are the aboriginal inhabitants of Norway and Fennoscandinavia and are ethnically different from the Norwegians. Different distribution of various immune-related diseases among the Samis compared with Norwegians have been reported. This is the first study to evaluate the distribution of IL-10 polymorphisms in the Sami population. Two hundred healthy Samis were genotyped for polymorphisms in the promoter region of IL-10 at region -1082 (G/A), -819 (T/C) and -592 (A/C). The allele frequencies, genotypes and haplotypes were compared with 187 healthy Norwegians. A significantly higher number of the Samis than the Norwegians had the ATA/ATA genotype, whereas the Norwegians displayed a higher frequency of the GCC/GCC genotype (P=0.0057). There was a significant difference in haplotypes in the two populations with a P=0.0024. These findings may be important for the distribution and clinical outcome of various infectious and immune-related disorders in the two populations.     

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.     

白细胞介素10启动子基因多态性与强直性脊柱炎的易感性

背景：在强直性脊柱炎患者中,基因多态性很可能影响细胞因子的分泌模式。 目的：在中国胶东半岛地区汉族人强直性脊柱炎患者中,探讨白细胞介素10启动子基因的单核苷酸多态性和单体型与强直性脊柱炎易感性的相关性。 方法：用酶联免疫吸附测定法测定血清中白细胞介素10的水平,用聚合酶链反应和限制性片段长度多态性方法对白细胞介素10基因启动子中的-1082A/G、-819C/T和-592C/A位点的单核苷酸多态性进行分析。 结果与结论：收集了110例强直性脊柱炎患者和120例同种族的健康人,强直性脊柱炎患者组血清中白细胞介素10水平明显高于健康对照组(Z=10.9,P < 0.001),单核苷酸多态性分析显示：在强直性脊柱炎患者组和健康对照组之间-592A/C位点基因型分布和等位基因频率没有明显差异,该研究中没有发现-1082GG基因型。强直性脊柱炎患者-1082G等位基因频率较健康对照组增加(P=0.047),通过logistic回归分析,强直性脊柱炎患者-1082AG基因型的比值比为1.993(95%CI：1.046-3.800,P=0.034 ),而-819CC基因型的比值比为3.125(95%CI：1.246-7.836,P=0.015),此外,单体型分析显示与ATA 基因型相比,GCC基因型显著增加了患强直性脊柱炎的风险(OR=2.19,95%CI：1.13- 4.26,P= 0.020)。结果表明白细胞介素10的基因单体型与中国胶东半岛地区汉族人强直性脊柱炎的易感因素相关。     

Cytokine gene polymorphisms and graft-versus-host disease in children after matched sibling hematopoietic stem cell transplantation: a single-center experience

Various polymorphisms in cytokine genes have recently been investigated as candidate risk factors in allogeneic hematopoetic stem cell transplantation (allo-HSCT). We retrospectively analyzed specific polymorphisms in genes for interleukin (IL)-10, IL-6, tumor-necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) in a pediatric cohort of 57 histocompatibility leucocyte antigen (HLA)-identical sibling myeloablative transplants. Both recipient and donor genotypes were tested for association with graft-versus-host disease (GVHD) by statistical methods including Cox regression analysis. We found a significant association between the IL-10 promoter haplotype polymorphisms at positions -1082, -819 and -592 with the occurrence of severe (grades III-IV) acute GVHD (aGVHD). Recipients with the haplotype GCC had a statistically significant decreased risk of severe aGVHD (hazard risk (HR)=0.20, 95% confidence interval (CI): 0.06-0.67) in comparison with patients with other IL-10 haplotypes (P=0.008). Transplant-related mortality at 1 year was significantly lower in recipients with this haplotype (HR=0.17, 95% CI: 0.012-0.320) versus other IL-10 haplotypes (P=0.03), whereas overall survival was not influenced by IL-10 haplotype polymorphisms. In multivariate analysis, the presence of the IL-10 GCC haplotype was found as the only variable associated with a statistically significant decreased hazard of severe aGVHD development (P=0.02, HR=0.21, 95% CI: 0.05-0.78). These results suggest that pediatric patients possessing the IL-10 GCC haplotype may be protected from the occurrence of severe aGVHD in the setting of matched sibling HSCT.     

Interleukin-10 promoter polymorphism in sporadic Alzheimer's disease

Proinflammatory cytokines and acute-phase proteins play an important role in Alzheimer's disease (AD) neurodegeneration, and common polymorphisms of genes controlling their high production have been shown to be associated with AD. Thus, AD patients display a proinflammatory genotype and the control of inflammation might play a protective role in AD development. By sequence-specific probes, we have evaluated the role of anti-inflammatory cytokine interleukin(IL)-10 in AD, by analysing in 132 AD patients and 213 healthy controls the prevalence of three different haplotypes, involving three single-nucleotide polymorphisms (SNPs) at -1082 (G-->A), -819 (C-->T) and -592 (C-->A) nucleotides of IL-10 promoter, associated with different IL-10 production. The percentage of -1082A carrier subjects was significantly increased among AD patients, and this increase was mainly due to the increase of ATA haplotype. Analysing these results according to the well-known genetic risk factor APOE-e4 allele, no significant differences were observed in SNP IL-10 allele distribution between AD patients carrying the genotype or not. So we may conclude that the presence of -1082A allele and in particular of -1082A/-819T/-592A haplotype, associated with a low production of anti-inflammatory cytokine IL-10, may be considered as an additive and independent genetic risk factor for AD.     

Interleukin-10 promoter polymorphisms in Chinese patients with Parkinson's disease

Interleukin-10 (IL-10), an important anti-inflammatory cytokine, may influence the risk for the development of onset of sparadic Parkinson's disease (PD) in the inflammatory process. In this study, two DNA polymorphisms at IL-10 gene promoter (-819 T/C and -592 A/C) were examined in 355 sporadic PD patients and 200 healthy controls in Han Chinese Population. For both polymorphisms, no significant difference in genotype or allele distribution was found between PD patients and the controls. For -819 T/C polymorphisms, there was significant difference in genotype distribution between EOPD (EOPD, <50 years of age) patients and each healthy-matched control subgroup (P=0.011), as well as between female PD patients and each healthy-matched control subgroup (P=0.024), For -592 A/C polymorphisms, there were no significant gender- and age-related differences in genotype distribution between PD patients and the controls subgroup. Results from our study revealed that the IL-10 promoter (-819 and -592) polymorphism is not a risk factor of sporadic Parkinson's disease, but the IL-10 promoter -819 polymorphism is a risk factor of EOPD and female PD patients in Han Chinese population.     

Association of -592C/A, -819C/T and -1082A/G interleukin-10 promoter polymorphisms with idiopathic recurrent spontaneous abortion

Increasing evidence supports a role for altered T helper 1 (Th1)-Th2 cytokine balance in idiopathic recurrent spontaneous abortion (RSA). The aim of this study was to investigate the association of the interleukin 10 (IL-10) promoter polymorphisms -592C/A, -819C/T and -1082A/G with RSA. Women (n = 350) with at least three consecutive spontaneous abortions (RSA cases) and 200 control women with at least two successful pregnancies were included. The frequency of the -819T allele [P = 0.05, odds ratio (OR) = 1.51], but not other single-nucleotide polymorphisms (SNPs), was higher among RSA patients. Complete linkage disequilibrium (LD) was seen between -592C and -819C and -1082G alleles, as well as between -592A and -819T and between -819C and -1082G alleles only among patients. Although the genotype frequencies (except for -819C/C) of the three polymorphisms were comparable between patients and controls, higher frequency of -592A/-819T/-1082A haplotype (OR = 4.01, 95% CI = 1.83-7.95) was seen in cases versus controls. Regression analysis indicated that, after adjusting for potential variables, -592C/A (OR = 3.32, 95% CI = 1.76-6.27) and -819C/T (OR = 5.06, 95% CI = 2.59-9.91) were associated with exclusively early but not exclusively late RSA, where negative association for both was noted. This supports the notion of involvement of IL-10-592C/A and -819C/T polymorphisms as inherited risk factors of idiopathic RSA.     

Genetic contribution of the interleukin-10 promoter polymorphism in endometriosis susceptibility

PROBLEM: Interleukin-10 (IL-10) is an important immunomodulatory cytokine. The aim of this study was to investigate whether polymorphisms of the IL-10 gene promoter polymorphisms may be responsible in part for genetic susceptibility to endometriosis. METHODS OF STUDY: Polymorphisms at position -1082 and -592 in the IL-10 promoter region were determined in 196 patients with endometriosis and 160 fertile healthy women by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). RESULTS: There were no statistically significant differences in the genotype and allele frequencies of IL-10 promoter polymorphism between the endometriosis and control groups. However, when subgrouped according to clinical features, the frequencies of the -592*CC genotype and -592*C allele were significantly increased in patients with autoantibodies to carbonic anhydrase II (anti-CA II ab) compared with controls. CONCLUSION: IL-10 promoter polymorphisms were associated with the production of anti-CA II ab in patients with endometriosis, suggesting a role in the genetic susceptibility for endometriosis.     

Interleukin 10 gene promoter polymorphisms in women with early-onset pre-eclampsia

Pre-eclampsia is one of the most serious disorders of human pregnancy and T helper type 1 (Th1)/Th2 imbalance plays a major role in its aetiology. The Th2 cytokine, interleukin (IL)-10, plays a significant role in the maintenance of pregnancy. The present study is aimed at understanding the role of IL-10 promoter polymorphisms (−1082 G/A; −592 A/C and −819 C/T) and their haplotypes in early-onset pre-eclampsia. A total of 120 patients and an equal number of women with normal pregnancy, from Government Maternity Hospital, Petlaburz, Hyderabad, India, were considered for the present study. A standard amplification refractory mutation system–polymerase chain reaction (ARMS–PCR) was carried out for genotyping followed by agarose gel electrophoresis. Appropriate statistical methods were applied to test for the significance of the results. It was found that the IL-10 −819 C allele (P = 0·003) and −592 A (P = 0·005) allele frequencies increased significantly in patients compared to controls. No significant difference was found with regard to −1082 promoter polymorphism. Haplotype analysis of the IL-10 single nucleotide polymorphisms (SNPs) revealed a significant association with ACC haplotype with a twofold increased risk in patients compared to controls. The frequencies of two common IL-10 haplotypes (GCC and ATA) did not show any significant difference. Further, the diplotype analysis revealed five genotypes: −1082A with −819C (P = 0·0016); −1082G with −819C (P = 0·0018); −819C with −592C (P = 0·001); −1082A with −592C (P = 0·032); and −1082G with −592C (P = 0·005) associated with the disease. These findings support the concept of contribution of IL-10 gene polymorphisms in the pathogenesis of early-onset pre-eclampsia.     

Relation of interleukin-10 Promoter Polymorphisms to Adult Chronic Immune Thrombocytopenic Purpura in a Cohort of Egyptian Population

Background: Adult chronic immune thrombocytopenic purpura (chronic ITP) is an autoimmune multifactorial bleeding disorder that occurs because of enhanced peripheral platelet destruction. Treatment decisions can be challenging because the goal of treatment is to prevent severe bleeding, but the risk of bleeding can be difficult to estimate for any individual patient.

Objective: This case–control study was planned to investigate the relationship of interleukin (IL)-10 promoter (IL-10-1082, -819 and -592) polymorphisms with the susceptibility, severity and outcome of adult chronic ITP in a cohort of Egyptian population.

Subjects and Methods: Typing of IL-10 promoter polymorphisms was done using restriction fragment length polymorphism for 62 adult patients with chronic ITP and 73 age- and sex-matched healthy controls.

Results: No significant differences were found between ITP patients and controls regarding the frequency of IL-10 promoter genotypes, alleles or haplotypes. IL-10-592 AA genotype and ATA (IL-10-1082, -819 and -592) haplotype were associated with severe ITP (p?=?0.003, 0.043, respectively).

Conclusion: Our findings suggest that the IL-10 promoter polymorphisms are unlikely to affect the development or treatment outcome of chronic adult ITP in Egyptian population, but IL-10-592 AA genotype and IL-10 (-1082, -819 and -592) ATA haplotype may be associated with disease severity. Because ITP is a complex disease, it is recommended that a multicenter study should be done with large sample size and unified typing technique.     

IL-10 promoter polymorphisms influence disease severity and course in psoriasis

We analyzed three single-nucleotide polymorphisms (SNPs) at the interleukin-10 (IL-10) 5' flanking region (positions -1082 A/G, -819 C/T and -592 C/A) in an association case-control study involving 248 patients with plaque type of psoriasis and 148 unrelated healthy volunteers using ARMS (amplification refractory mutation system)-PCR (Polymerase Chain Reaction) method. No difference was found in the frequencies of haplotype distribution between healthy controls and patients with psoriasis. There were no significant differences in the IL-10 haplotype distribution depending on the age of onset and family history of psoriasis. However, the results of our study demonstrate that the IL-10 haplotype has a role in determining severity and course of plaque type of psoriasis. IL-10 ACC haplotype (P<0.05) is likely to be defining lower activity of disease (PASI相似文献   

Promoter haplotypes of the interleukin-10 gene influence proliferation of peripheral blood cells in response to helminth antigen

Since interleukin (IL)-10 is a key mediator of immunosuppression, and immunosuppression is considered an important element of helminth infection, we studied variants of the putative IL-10 gene promoter in 337 individuals from 130 families heavily exposed to infection by the tissue nematode Onchocerca volvulus. As shown by transmission disequilibrium tests, variants of the IL-10 promoter at positions -1082(G/A), -819(C/T), and -592(C/A) in the haplotype of ATA were significantly associated with high peripheral blood cell (PBC) proliferative responses to O. volvulus antigen (OvAg). No associations were observed using phytohemagglutinin-induced PBC proliferation or with qualitative or quantitative phenotypes of onchocerciasis or onchocerciasis-related skin disease. The findings are compatible with the hypothesis that the ATA haplotype causes a decrease in IL-10 production by OvAg-reactive type-1 regulatory T-lymphocytes, thereby alleviating the suppression of other T cells. To our knowledge, this is the first time that an influence of IL-10 promoter variants is shown on the adaptive immune response.