白介素-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。该文主要评述白介素-10基因多态性与乙肝病毒感染的关系。     

白介素-10（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     

肿瘤坏死因子基因多态性与感染性疾病

位于人类主要组织相容性复合体Ⅲ类基因区内的TNF基因具有多种多态性 ,这些多态性可从转录水平影响TNF的表达产量 ,并与个体对感染性疾病的易感性、发展、预后相关 ,探讨以TNF基因多态性为代表的免疫基因因素与感染性疾病的关系 ,不仅可以寻找判断预后的基因标志 ,还可以为感染性疾病的免疫基因治疗奠定基础。     

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。     

白介素10的基因多态性与尖锐湿疣的相关性研究

目的探讨白介素10（IL-10）基因启动子-1082位点基因多态性与尖锐湿疣的相关性。方法采用焦磷酸测序法（Pyrosequencing）检测30例尖锐湿疣患者（观察组）和50例健康体检者（对照组）IL-10基因启动子-1082G/A位点基因型和等位基因频率;同时采用双抗体夹心ELISA法测定对照组和观察组的血清IL-10水平。结果观察组血清IL-10水平显著高于对照组（P〈0.01）。观察组IL-10基因启动子-1082 G/A位点GG基因型分布频率和G等位基因频率高于对照组（P〈0.01）。在观察组中表达GG基因型患者的血清IL-10水平显著高于表达其它基因型患者的血清IL-10水平（P〈0.05）。结论 IL-10基因多态性与尖锐湿疣易感性可能相关,IL-10基因启动子-1082 G/A位点GG基因型携带者对尖锐湿疣的易感性高。     

白介素-1受体拮抗剂基因多态性与散发性帕金森病的关系

目的探讨白介素-1受体拮抗剂（IL-1RA）基因多态性与帕金森病（PD）的关系。方法本实验用PCR-片段长度多态性分析法检测了89例中国散发性帕金森病病人和67例正常对照的白介素-1受体拮抗剂基因多态性。结果与对照组相比,PD组中IL-1RA基因VNTR多态性的A2等位基因有增加的趋势,但两者差异无统计学意义（P〉0.05）。帕金森病合并痴呆组（PDD组）中IL-1RA基因A2等位基因频率较非痴呆组（PDND组）有显著性增加（P〈0.05）,而且在PDD组中,IL-1RA基因A2/A2纯合子和A1/A2杂合子基因型频率较PDND组有显著性增加（P〈0.05）。结论IL-1RA基因多态性可能与我国人散发性帕金森病的发病无关,而与帕金森病并发痴呆发病过程中有关。     

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。     

白细胞介素-10基因多态性与卵巢癌的相关性研究

目的探讨白细胞介素-10（IL-10）基因启动子区域-1082、-819和-592位点单核苷酸多态性与卵巢癌的关系。方法用序列特异性引物聚合酶链（PCR-SSP）技术,检测33例卵巢癌患者和90例正常对照组IL-10基因多态性。结果-819位点卵巢癌患者C/T基因型频率显著高于健康对照组（45.5%比21.0%,P〈0.05）,C/C和T/T基因型频率虽然低于对照组（分别为6.1%比20.0%和48.4%比59.0%）,但是差异无统计学意义（P〉0.05）;-592位点卵巢癌患者C/A基因型频率显著高于健康对照组（45.5%比21.0%,P〈0.05）,C/C和A/A基因型频率虽然低于对照组（分别为6.1%比20.0%和48.4%比59.0%）,但是差异无统计学意义（P〉0.05）;-1082位点基因型频率在卵巢癌患者和正常对照组间差异无统计学意义（P〉0.05）。-1082、-819、-592位点等位基因频率在卵巢癌患者和正常对照组间差异均无统计学意义。结论IL-10基因启动子区域-819C/T和-592C/A基因型可能与卵巢癌的发生有关。     

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。     

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。     

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.     

慢性重型乙型肝炎患者白细胞介素-10基因多态性相关性研究

目的研究白细胞介素-10(IL-10)基因启动子区域-1082、-819和-592位单核苷酸多态性与慢性重型乙型肝炎之间的关系。方法采用聚合酶链反应-限制性片段长度多态性分析法(PCR- RFLP)和聚合酶链反应-序列特异性引物扩增法(PCR-SSP)检测98例慢性重型乙型肝炎患者(CSH)、478例慢性乙型肝炎患者(CHB)、223例慢性HBV携带者(ASC)和267例自限性HBV感染者外周血单个核细胞(PBMC)基因组DNA IL-10基因启动子区域3个位点-1082、-819、-592的基因多态性,并进行统计学分析。结果IL-10-1082、-819、-592在慢性重型肝炎组与其它组比较差异有统计学意义:(1) -1082基因AA型在CSH中的检出频率显著高于ASC(χ2=13.314,P=0.001)及自限性感染者(χ2= 13.545,P=0.000);(2)-592基因AC、CC型在CSH中的检出频率显著高于CHB(χ2=15.970,P=0.000;χ2=20.414,P=0.000)、ASC(χ2=21.283,P=0.000;χ2=28.309,P=0.000)及自限性感染者(χ2 =17.047,P=0.000;χ2=16.528,P=0.000);(3)-819基因TC型在CSH中的检出频率显著高于CHB (χ2=58.961,P=0.000)、ASC(χ2=53.255,P=0.001)及自限性感染者(χ2=39.616,P=0.001),提示-1082基因AA型,-592基因AC、CC型及-819基因TC型与慢性重型肝炎的发生有关,说明-1082AA, -592CC、AC及-819TC基因携带者患慢性重型肝炎风险相对较大。结论IL-10启动子区基因多态性与HBV感染所致肝病的肝损害进展和重型肝炎的发生可能有关。     

天津地区汉族人群IL-10-592C/A基因多态性与冠状动脉支架术后再狭窄的关系

目的 探讨中国天津地区汉族人群白细胞介素-10(interleukin-10,IL-10)-592C/A基因多态性的功能性以及其对经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)术后再狭窄的发病,PCI术后血清IL-10水平的影响.方法 对437例接受PCI并进行冠状动脉造影随访的患者,按冠状动脉造影结果分为再狭窄组(166例)和非再狭窄组(271例),应用聚合酶链反应-限制性片段长度多态性方法检测IL-10-592位点基因型和等位基因频率的分布;用酶联免疫吸附试验法测定2组PCI术前及PCI术后24 h血清IL-10浓度,并比较两组间和各基因型间IL-10水平.结果 (1)IL-10-592C/A基因型和等位基因频率在再狭窄组和非再狭窄组之间差异无统计学意义(P均＞0.05);(2)PCI术后24 h血清IL-10水平再狭窄组显著低于非再狭窄组[(82.67±35.02)ng/Lvs.(95.08±32.26)ng/L,P＜0.05];(3)IL-10-592位点A等位基因携带者(AA+AC基因型)术后24 h血清IL-10水平明显低于非携带者(CC型)[(86.13±34.77)ng/L vs.(102.50±27.52)ng/L,P＜0.05];(4)再狭窄组A等位基因携带者术后24 h血清IL-10水平明显低于非携带者[(78.51±34.09)ng/L vs.(102.19±33.66)ng/L,P＜0.05];(5)再狭窄危险的多因素Logistie回归分析显示:急性冠状动脉综合征、术前狭窄程度、靶病变长度与冠状动脉内支架再狭窄呈正相关(()R值分别为5.90、1.86、2.83),术后24 h血清IL-10水平、参照血管直径、支架直径与冠状动脉内支架再狭窄呈负相关(OR值分别为0.99、0.70、0.46).结论 (1)IL-10基因-592 C/A多态性与中国天津地区汉族人群再狭窄发病无关;(2)IL-10是PCI术后早期的炎症细胞因子,术后24 h血清IL-10水平为再狭窄的独立预测因素,携带A等位基因的个体可能通过降低其表型血清IL-10水平而增加了冠状动脉内支架术后再狭窄的发病.

Abstract：

Objective To investigate the relationship of interleukin-10 gene (IL-10)polymorphism and the serum IL-10 level with restenosis after percutaneous coronary intervention (PCI) in Tianjin Chinese Han population and study the effect of IL-10 gene polymorphism on serum IL-10 level. Methods Four hundred and thirty-seven patients who successfully underwent PCI with a follow-up angiography were divided into a restenosis group (n= 166) and non-restenosis group (n= 271). The IL-10 gene promoter polymorphism at position -592 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Meanwhile their serum IL-10 level before and 24 h after PCI was determined by enzyme-linked immunosorbent assay (ELISA). Results (1) There was no significant difference in frequencies of -592 genotypes and alleles between the two groups (P＞0. 05); (2) The 24 hpost-PCI IL-10 serum level of restenosis group was significantly lower than that of the non-restenosis group [(82. 67±35. 02) ng/L vs. (95.08±32.26) ng/L, P＜0.05]; (3) The serum level of the A allele carriers (AA+AC) was significant lower than that of the CC carriers [(86.13±34.77) ng/L vs. (102. 50±27.52)ng/L,P＜0.05]; (4) In the restenosis group, the 24 h post-PCI serum level of IL-10 in the A allele carriers was also significantly lower than that in those without the A allele [(78.51 ± 34.09) ng/L vs. (102.19 ±33.66) ng/L, P＜ 0. 05]; (5) Logistic regression analysis revealed positive correlations between acute coronary syndrome patients, pre-PCI degree of stenosis, length of target stenosis lesion and restenosis (OR=5.90, 1.86, 2.83 respectively); and there were negative correlations between 24 h post-PCI serum level of IL-10, the stent diameter, the diameter of reference vessel before stent implantation and restenosis (OR=0. 99, 0. 70, 0. 46 respectively). Conclusion (1) TheIL-10 gene -592 C/A polymorphism was not associated with restenosis in the Tianjin Chinese Han population; (2) IL-10 is an early post-PCI inflammatory cytokine, 24 h post-PCI serum IL-10 level was an independent predictive factor for restenosis,the IL-10 A allele carriers may have increased incidence of in-stent restenosis (ISR) by reducing the serum IL-10 levels.     

贵州苗族、侗族、布依族人群白介素10基因-592与-819位点的多态性研究

目的 研究中国贵州世居少数民族苗族、侗族与布依族人群中白介素10 (IL-10)基因启动子区-592与-819位点的多态性,为进一步研究其与疾病的相关性提供依据.方法 对上述人群采用TaqMan-MGB探针实时荧光聚合酶链反应SNP分型技术分析IL-10-592与IL-10-819位点多态性.结果 IL-10-819基因型频率在贵州苗族与侗族、苗族与布依族中的分布差异有统计学意义(P＜0.05),而在侗族与布依族之间分布差异无统计学意义(P＞0.05),IL-10-819(C/T)位点在贵州苗族群体中具有较高的突变率.IL-10-592基因型频率在贵州苗族与侗族、苗族与布依族之间分布差异有统计学意义(P＜0.05),在贵州侗族与布依族之间分布差异无统计学意义(P＞0.05),贵州苗族群体中IL-10-592位点T等位基因频率远高于侗族与布依族群体.贵州苗族、侗族、布依族IL-10-592位点与IL-10-819位点的多态分布与希腊及巴西人群分布差异无统计学意义(P＞0.05),而与中国广州及台湾汉族人、韩国人、加拿大人群的分布差异有统计学意义(P＜0.05),IL-10-592 A与IL-10-819 T突变频率显著低于中国广州及台湾汉族人和韩国人群的突变频率,但又显著高于加拿大人群的IL-10-592 A与IL-10-819 T的突变频率.结论 IL-10-819与IL-10-592多态性位点在贵州世居少数民族苗族、侗族与布依族人群中有着不同的分布,而IL-10-819与IL-10-592位点在不同种族、地域的群体中分布亦有显著的差异.     

The interleukin-10 gene promoter polymorphism -1087AG does not correlate with clinical outcome in non-Hodgkin's lymphoma

The Interleukin 10 (IL-10) gene is highly polymorphic, and the IL-10(-1087AG) (rs1800896) gene variation is the only so far studied intensively in association with certain diseases. Conflicting data have been published about an association of IL-10(-1087AG) gene variation with lower rates of complete remission and lower overall survival (OS) in patients with diffuse large B-cell lymphoma. To further investigate this in malignant lymphoma, we established the IL-10 genotypes in patients from the NHL-B1/ B2 studies from the German High-Grade Non-Hodgkin's Lymphoma Study Group. In our study, allele frequencies of lymphoma patients are comparable as in healthy controls. No increase of IL-10(-1087G) alleles was found. In addition we did not find any difference in OS or event-free survival between patients with IL-10(-1087AA) and the other genotypes. Comparable results were obtained for the IL-10 loci at -3538 (A/T), -1354 (A/G), -824 (C/T) and -597 (A/C) (rs1800890, rs1800893, rs1800871 and rs1800872).     

The interleukin-10-1082 promoter polymorphism and cancer risk: a meta-analysis

Interleukin-10 (IL-10) is a multifunctional cytokine with both immunosuppressive and anti-angiogenic properties and play an important role in the pathogenesis of cancer. IL-10-1082A>G polymorphism is the most extensively studied polymorphism in the IL-10 gene in cancer susceptibility. To date, a number of case-control studies were conducted to investigate the association between IL-10-1082A>G polymorphism and cancer risk in humans. However, the association between the IL-10-1082A>G polymorphism and cancer risk is still ambiguous. In an effort to solve this controversy, we performed a meta-analysis based on 61 case-control studies, including 14,499 cancer cases and 16,967 controls. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. In the stratified analyses by specific cancer type, increased risk was found in lung cancer (OR = 3.16, 95% CI = 1.16-8.63 for GA versus AA; OR = 2.07, 95% CI = 1.16-3.70 for GG versus AA; OR = 3.17, 95% CI = 1.31-7.68 for GA/GG versus AA) and non-Hodgkin's lymphoma (OR = 1.18, 95% CI = 1.02-1.36 for GA versus AA; OR = 1.17, 95% CI = 1.02-1.35 for GA/GG versus AA). The meta-analysis also indicated that the variant genotypes were associated with a moderately increased risk in Asians in all genetic models (OR = 1.80, 95% CI = 1.17-2.76 for GA versus AA; OR = 3.32, 95% CI = 1.62-6.82 for GG versus AA; OR = 1.67, 95% CI = 1.07-2.60 for GA/GG versus AA; OR= 2.93, 95% CI = 1.43-6.03 for GG versus AA/GA). The meta-analysis suggested that the IL-10-1082A>G polymorphism was associated with increased risk of cancer in Asians and lung cancer and non-Hodgkin's lymphoma. To draw comprehensive and true conclusions, more researches with larger numbers of worldwide participants are needed to examine associations between IL-10-1082A>G polymorphism and cancer risk.     

IL-10 gene polymorphism and herpesvirus infections

Genetics has an important role in resistance to various infections and it also may modify the clinical picture of an infectious disease. Here, we briefly review our recent data demonstrating that the polymorphism of the IL-10 gene is associated with resistance to some common herpesviruses and, additionally, that this same gene is involved in the regulation of the severity of the infection and in the reactivation process.     

IL-10基因修饰的大鼠树突状细胞表型分析及生物学特性的研究

目的研究IL-10基因修饰后的大鼠树突状细胞(DC)的表型及其生物学特性。方法以含IL-10基因的重组腺病毒载体体外转染大鼠骨髓来源的DC,Western blot测定转染后各组DC中IL-10蛋白的表达,流式细胞仪检测各组DC表面抗原CD83、CD86分子的表达情况,混合淋巴细胞反应法测定各组DC刺激同种异体T细胞增殖的能力。结果 IL-10基因修饰组DC可检测到IL-10高表达,表面抗原CD83、CD86低表达,其刺激T淋巴细胞增殖水平较其他各组低。结论 IL-10基因修饰的DC可有效的表达有功能的IL-10,为研究IL-10修饰的DC诱导同种异体移植免疫耐受奠定了基础。