白介素-10（IL-10）与乙肝易感性相关性研究

细胞因子在抗病毒免疫中发挥着重要的作用。细胞因子的基因多态性能影响个体间细胞因子水平上的差异，从而导致个体间对于乙肝病毒感染免疫应答的差异，影响个体对乙肝病毒的易感性。本文主要评述白介素-10基因多态性与乙肝病毒感染的关系     

白介素-10基因多态性与感染性疾病的关系的研究进展

白介素-10(interluekin-10 IL-10)是一种具有抗炎和免疫调节作用的细胞因子。是同型二聚体细胞因子, 属长链细胞因子家族。现已发现B细胞、单核／巨噬细胞、肥大细胞、角化细胞、肝细胞及多种肿瘤细胞均可分泌IL-10。 IL-10通过调节其他细胞因子的作用而起到抗炎和免疫调节作用。我们在这里主要谈一下,IL-10的生物学特点及在IL- 10基因的启动子区域几个位点的基因多态性与感染性疾病的关系的研究进展。     

白介素-23受体基因多态性与乙肝相关肝细胞癌的易感性研究

目的:探讨白介素-23受体(IL-23R)基因多态性与广西壮族人群乙肝相关肝细胞癌(HCC)易感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对84例乙肝表面抗原(HBSAg)阳性HCC患者(病例组)和94例HbsAg阳性体检者(对照组)IL-23R基因rs10889677、rs1884444、rs114658173个位点的单核苷酸多态性进行检测及其部分标本进行直接测序鉴定。采用SHEsis软件构建IL-23R基因3个位点的单体型。Logistic回归分析IL-23R基因多态性和单体型与HCC遗传易感性的关系。结果:IL-23Rrs10889677、rs11465817位点的AA、AC、CC3种基因型和A、C两种等位基因在HCC组与对照组之间的分布差异无统计学意义(P>0.05)。rs1884444位点的TT、TG、GG三种基因型及T、G两种等位基因在病例组和对照组的频率分布差异均有统计学意义(P均<0.05),Logistic回归分析发现携带TG基因型的个体发生HCC的风险较携带TT基因型的个体增加(校正OR=2.20,95%CI=1.11～4.37)。单体型构建发现CGC、AGC、CTC、ATC、CGA、AGA、CTA、ATA等8种单倍体,病例组和对照组的AGC单倍体分布差异有统计学意义(P<0.05),AGC单倍体携带者发生HCC的风险明显增加(校正OR=2.71,95%CI=1.06～6.93)。结论:IL-23R基因rs1884444位点TG基因型可能是HCC发病的危险因子;乙肝背景下AGC单倍体携带者患HCC的风险增加2.71倍,可能是乙肝相关肝癌发病的危险因素。     

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。     

白介素10家族研究近况

从白介素10家族的发现、结构特征、各成员概况和生物学活性、与疾病的关系以及前景展望等方面综述了白介素10家族各成员的研究近况。     

白介素10家族研究近况

从白介素10家族的发现、结构特征、各成员概况和生物学活性、与疾病的关系以及前景展望等方面综述了白介素10家族各成员的研究近况。     

白介素-10与心血管疾病

1989年Fiorentino等发现Th2细胞能产生一种细胞因子合成抑制因子（CSIF），后拟名为白介素10（IL-10），它能有效地抑制Th1细胞的功能。近年研究表明：IL-10不仅与自身免疫性疾病、感染性疾病密切相关，且参与了部分心血管疾病的发病过程。     

白介素-32 基因多态性及血清水平与多发性硬化遗传易感性的关联性

目的:探讨IL-32 基因rs28372698A/ T、rs12934561C/ T 及rs11861531C/ T 三个位点的多态性与多发性硬化(MS)的遗传易感的关系,为MS 高危人群的确立提供理论依据。方法:入选580 例MS 患者和650 例健康对照,应用单碱基延伸法和DNA 测序对IL-32 基因位点进行基因分型,同时,采用酶联免疫吸附试验检测两组IL-32 的血清浓度。结果:IL-32 基因rs28372698A/ T 位点的基因型频率和对照组比较存在显著差异(P =0.007),其等位基因频率在两组间的分布频率存在统计差异(P =0.033)。rs12934561C/ T 与rs11861531C/ T 的各基因型及等位基因频率在两组间差异无统计学意义(P>0.05)。T-T-T单倍型在HCC 中的分布频率显著高于对照组(P = 0.012),T-T-T 单倍型与MS 的发病风险密切相关(OR = 1.968,95% CI:1.352-2.574)。MS 患者组的血清IL-32 水平明显高于对照组[(399.08±156.85)pg/ ml vs(239.99±88.35)pg/ ml,P =0.001]。AT 和TT 基因型的MS 患者IL-32 血清水平明显高于AA 基因型MS 患者[(465.53 ±172.40) pg/ mL vs (295.86 ±103.96)pg/ ml,P<0.01;(491.15±133.65)pg/ ml vs (295.86±103.96)pg/ ml,P<0.01]。结论:本研究首次报道了IL-32 基因rs28372698 位点多态性与MS 的关系,且IL-32 的基因多态性在MS 患者中对IL-32 的血清水平有影响。我们的研究为MS 遗传和个体化的诊疗提供了新的参考依据。     

IL-10 基因多态性与溃疡性结肠炎易感性的关系及对临床预后的影响

目的:探讨IL-10 多态位点的基因多态性与溃疡性结肠炎的易感性及对临床预后的影响。方法:采用病例对照研究设计,选取80例溃疡性结肠炎患者作为病例组,另外选性别和年龄匹配的健康受试者作为对照组。所有患者治疗前抽取空腹静脉血并提取DNA,设计819 T/ C(rs1800871)、592A/C(rs1800872)、 -1082 G/ A(rs1800896)PCR 引物进行PCR 扩增,扩增产物酶切后进行琼脂糖凝胶电泳以确定基因类型,采用Logistic 回归计算校正相对危险度(OR)和95% 置信区间(95%CI)评价基因多态性与溃疡性结肠炎的易感性,并分析对临床预后的影响。结果:(1) 病例组患者IL鄄10 多态位点rs1800896 基因类型AA、GG 和AG 分布频率与对照组受试者差异具有统计学意义(P<0.01);(2)与rs1800896 基因型AA 比较,基因型为GG 的患者溃疡性结肠炎危险性显著升高(P<0.01),并且临床缓解率显著降低(P<0.01);(3)病例组患者IL-10多态位点rs1800871 基因类型CC、CT 和TT 分布频率与对照组受试者差异无统计学意义(P>0.05);(4)病例组患者IL鄄10 多态位点rs1800872 基因类型AA、AC 和CC 分布频率与对照组受试者差异无统计学意义(P>0.05)。结论:IL-10 多态位点rs1800896 基因类型GG 可增加溃疡性结肠炎的易感性,并且显著降低患者的临床预后。     

屋尘螨过敏性哮喘患者白介素-2和白介素-4血清水平及基因多态性

目的:检测分析屋尘螨过敏性哮喘患者白介素-2(IL-2)、IL-4血清水平及基因多态性。方法:首次诊断为屋尘螨过敏性哮喘患者73例(过敏性哮喘组),按其临床表现再分为急性发作期组(n=25)、慢性持续期组(n=23)和临床缓解期组(n=25),另选体检健康人群作为对照组(n=81)。采用ELISA检测各组血清IL-2、IL-4和屋尘螨特异性IgE(SIgE)水平,采用等位基因特异性PCR检测各组IL-2基因rs6534349和IL-4基因rs2227284的单核苷酸多态性(SNP)位点基因多态性。结果:血清IL-2水平在急性发作期组(170.58±29.08pg/ml)及慢性发作期组(179.45±45.34pg/m)均较对照组(227.45±43.34pg/ml)明显降低(P0.01);两组血清IL-4水平分别为98.45±28.85pg/ml和89.34±39.21pg/ml,均较对照组(68.41±30.01pg/ml)明显升高(P0.05);临床缓解期组血清IL-2和IL-4水平与对照组差异无统计学意义(P0.05)。血清SIgE水平在急性发作期组(21.27±2.96pg/ml)、慢性持续期组(19.45±10.38pg/ml)和临床缓解期组(18.34±4.21pg/ml)均明显高于对照组(8.90±4.00pg/ml)(P0.01)。SIgE水平变化与IL-2变化呈负相关(r=-0.421,P0.01),与IL-4变化呈正相关(r=0.522,P0.01)。基因多态性分析显示,过敏性哮喘组患者IL-2rs6534349中GG型明显低于对照组(P0.01),而IL-4rs2227284CC型明显高于对照组(P0.01)。结论:屋尘螨过敏性哮喘与其血清IL-2、IL-4水平及基因多态性具有一定关系。     

CCR5基因多态性与乙型肝炎病毒感染相关性的研究进展

趋化性细胞因子和趋化性细胞因子受体在抗病毒免疫中发挥了重要作用。乙型病毒性肝炎是由其表达的抗原系统及其抗体所介导的特异性免疫反应和非特异性的以细胞因子为主的炎症介质导致的肝细胞损伤。CCR5作为趋化性细胞因子受体在乙型病毒性肝炎的发生发展中起重要作用。本文主要讲述CCR5基因的结构和功能,及在编码区和启动子区的多态性与HBV感染的相关性研究。     

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.     

Interleukin-10 Gene Polymorphisms in Recurrent Aphthous Stomatitis

Recurrent aphthous stomatitis (RAS) is a common oral inflammatory disease with unknown etiology in which the immune system seems to have a role in oral tolerance. Interleukin (IL)-10 is a cytokine synthesis inhibitory factor. Single nucleotide polymorphisms (SNPs) of IL10 gene could alter this cytokine production. The aim of this study was to investigate frequencies of IL10 alleles and genotypes in a group of individuals with RAS. Genomic DNA of 60 Iranian patients with RAS were typed for IL10 gene (C/A ?1082, C/T ?819, and C/A ?592), using PCR-SSP method. Frequency of each allele and genotype was compared to control group.

A significantly higher frequencies of the T allele at position ?819 (p?=?0.006) and the A allele at position of ?592 (p?<?0.001) were found in the patients with RAS group, when compared to the controls. IL10 GA genotype at position ?1082 (p?=?0.007), CA genotype at position ?592 (p?=?0.001), and CT genotype at position ?819 (p?=?0.001) were significantly higher in the RAS patients. The results of this study suggest that certain SNPs of IL10 gene have association with predisposition of individuals to RAS. However, further multicenter studies should be conducted to confirm the results of this study.     

Association of Single Nucleotide Polymorphisms of the Interleukin-10 Promoter Gene and Susceptibility to Primary Biliary Cirrhosis: Immunogenetic Differences in Italian and Japanese Patients

Several lines of data suggest that genetic factors play an important role in the onset and/or progression of primary biliary cirrhosis (PBC). Since PBC is an autoimmune disease, it is reasoned to assume that genes encoding cytokines may confer susceptibility to disease. Amongst these factors, interleukin-10 (IL-10) has received significant attention. The promoter region of IL-10 gene has three single nucleotide polymorphisms (SNPs) at positions &#109 1082, &#109 819 and &#109 592. To elucidate the association of the three SNPs of IL-10 promoter region with susceptibility of PBC in two different genetic populations, 159 unrelated patients with PBC (94 Italian and 65 Japanese) and 143 local controls (72 Italian and 71 Japanese) were enrolled. SNPs were determined using allele-specific PCR/RFLP. In Italian PBC patients, the frequency of homozygosity for G/G at position &#109 1082 was significantly higher than that of local controls (p <0.041, OR=2.44, 95% C.I.; 1.02-5.86). The frequencies of haplotype GCC in PBC patients, possibly linked to higher IL-10 production, were also significant higher than local controls (p <0.033). However, in Japanese population, there were no significant differences in the three SNPs and haplotypes between PBC patients and controls. Excessive production of IL-10 may play an important role in some populations in modulating the onset of PBC. Further, immunogenetic studies of PBC should take into account ethnic and geographic variations; this makes such studies in heterogeneous population, like the USA, more difficult.     

Association of Interleukin-10 gene promoter polymorphisms in Saudi patients with vitiligo

The promoter region of human Interleukin -10 gene is highly polymorphic and has been associated with numerous autoimmune diseases. Recent studies have linked vitiligo with defective autoimmune system. This study is aimed to explore a possible association between IL-10 gene polymorphism and vitiligo in Saudi population. This case control study consisted of 184 Saudi subjects including 83 vitiligo patients (40 males, 43 females mean age 27.85 +/- 12.43 years) and 101 matched controls. Genomic DNA was extracted from the blood samples of healthy controls and Vitiligo patients visiting out patient clinic of Department of Dermatology, Riyadh Armed Forces Hospital, using QIA ampR DNA mini kit (Qiagen CA, USA). Interleukin-10 gene was amplified by polymerase chain reaction (PCR) using Arms primers to detect any polymorphism involved at positions -592, -819 and -1082. The frequencies of GG genotype at -1082, and CC genotype at positions -592 and 819 were significantly higher in vitiligo patients compared to healthy subjects suggesting that GG and CC genotypes might be susceptible to vitiligo in Saudis. On the other hand genotypes -1082 GA, -819 CT, and -592 CA of IL-10 were more prevalent in healthy controls suggesting protective effects of GA, CT and CA genotypes against vitiligo. This study indicates that the IL-10 gene may play a significant role in the etiology of vitiligo among Saudis.     

Impact of Interleukin-10 Gene Polymorphisms on Survival in Patients with Colorectal Cancer

Chronic inflammation is thought to be the leading cause of colorectal cancer, and interleukin-10 (IL10) has been identified as a potent immunomodulatory cytokine that regulates inflammatory responses in the gastrointestinal tract. Although several single nucleotide polymorphisms (SNPs) in IL10 have been associated with the risk of colorectal cancer, their prognostic significance has not been determined. Two hundred and eighty-two colorectal cancer patients were genotyped for two candidate cancer-associated SNPs in IL10. The associations of these SNPs with distant metastasis-free survival and overall survival were evaluated by Kaplan-Meier analysis and Cox regression model. The minor homozygote GG genotype of IL10 rs3021094 was significantly associated with a 3.30-fold higher risk of death compared with the TT+TG genotypes (P=0.011). The patients with IL10 rs3021094 GG genotype also had a poorer overall survival in Kaplan-Meier analysis (log-rank P=0.007) and in multivariate Cox regression model (P=0.044) adjusting for age, gender, carcinoembryonic antigen levels, tumor differentiation, stage, lymphovascular invasion, and perineural invasion. In conclusion, our results suggest that IL10 rs3021094 might be a valuable prognostic biomarker for colorectal cancer patients.     

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.     

Association of G-174C Polymorphism of the Interleukin-6 Gene Promoter with Graves' Ophthalmopathy

Interleukin-6 (IL-6) may play an important role in the pathogenesis of Graves' ophthalmopathy (GO). The aim of this study was to analyze the association of IL-6 gene promoter polymorphism, at position -174 (G→C, termed as G-174C), which may affect IL-6 production, with the development of GO. The G-174C polymorphism was determined in 279 Polish-Caucasian patients with Graves' disease (GD), of which 108 had clinically evident ophthalmopathy (NOSPECS class III or higher) and 186 healthy Polish adults. In patients with GD, the frequencies of the C allele (45 vs 42%; P=0.35) and C/C genotype (20 vs 15%; P=0.13) were not significantly different compared to controls. Subdividing patients with GD for the presence of eye disease revealed that the C allele (44 vs 45%; P=0.76) and C/C genotype (20 vs 20%; P=0.92) were equally distributed in patients with or without ophthalmopathy. There was also no association between the G-174C polymorphism and the severity of eye changes. Finally, IL-6 genotypes were not associated with laboratory findings (thyroid volume, serum IL-6 and thyroid autoantibodies levels) in patients with GD at diagnosis. Our results suggest that G-174C polymorphism of the IL-6 gene does not contribute to the development and severity of GO.     

Interleukin-4 and Interleukin-10 Gene Polymorphisms in Patients with Inflammatory Bowel Disease

Background: Changes in cytokine expression have been frequently found in patients with inflammatory bowel disease (IBD). Cytokine values outside the normal range may be somewhat related to common polymorphisms within cytokine genes.

Objective: The present study was designed to investigate the possible association between polymorphisms within Interleukin IL-4 and IL-10 genes and susceptibility to and clinical features of IBD.

Methods: The study population was composed of 140 healthy controls and 75 patients with IBD (40 patients with Crohn’s disease (CD) and 35 patients with ulcerative colitis (UC)). Genotyping was performed using polymerase chain reaction with sequence-specific primers.

Results: Higher frequencies for the C allele of IL-4–590 polymorphism (P < 0.0001; odds ratio [OR], 5.68; 95% confidence interval [95% CI], 3.28–9.83) and for the T allele of IL-4–1098 polymorphism (P = 0.016; OR, 1.83; 95% CI, 1.11–3.02) were observed in the whole group of IBD patients. The IL-4–590 C allele was also significantly overrepresented when IBD patients were subdivided into CD and UC (P < 0.0001; OR, 5.2–6.28). While the IL-4–1098 T allele was present at higher frequencies in patients with UC (P = 0.05; OR, 1.95), but not in CD (P = 0.09). Multiple pairwise comparisons indicated that genotypes of all polymorphisms investigated within IL-4 gene are correlated with IBD, CD, and UC. Haplotype analysis showed that the IL-4–1098/-590 TC haplotype might predispose individuals to IBD, CD, and UC whereas the IL-4–1098/-590 TT and GC haplotypes have a protective effect. On the contrary, neither allele nor genotype frequencies of IL-10 polymorphisms (IL-10–1082 A > G, IL-10–592 A > C, and IL-10–819 T > C) were associated with IBD, CD, or UC.

Conclusions: The present study suggests that IL-4 polymorphisms might play a role in susceptibility to IBD and its major subtypes in the Iranian population.     

Association of Interleukin-10 A-592C Polymorphism in Taiwanese Children with Kawasaki Disease

Elevated serum levels of interleukin-10 (IL-10) have been reported in patients with Kawasaki disease (KD). IL-10 reduces the inflammatory actions of macrophages and T cells and it may play a significant role in the regulation of inflammatory vascular damage associated with systemic vasculitis. The aim of this study was to examine whether -592 IL-10 promoter polymorphism is a susceptibility or severity marker of KD in Chinese patients in Taiwan. The study included 105 KD patients and 100 normal controls. Genotype and allelic frequencies for the IL-10 gene polymorphism in both groups were compared. There were no significant between-group differences in the genotype distribution of IL-10 A-592C gene polymorphism (P=0.08). However, the frequency of the -592*A allele was significantly increased in the patients with KD compared with controls (71.9% vs. 61.0%, P=0.019). The odds ratio for developing KD in individuals with IL-10-592*A allele was 1.64 (95% confidence interval, 1.06-2.52) compared to individuals with the IL-10-592*C allele. No significant difference was observed in the genotype and allelic frequencies for the IL-10 A-592C polymorphism between patients with and without coronary artery lesions. The IL-10-592*A allele may be involved in the development of KD in Taiwanese children.