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。     

IL-4R、IL-13、ADAM33基因多态性与中国皖南地区汉族人群支气管哮喘的相关性研究

目的:探讨IL-4受体基因Arg551Gln(rs1801275)、IL-13基因Arg130Gln(rs20541)、ADAM33基因T1(rs2280091)位点基因多态性与中国皖南地区汉族人群支气管哮喘的相关性。方法:采用病例-对照的方法,用聚合酶链反应及直接基因测序法比较116例支气管哮喘组与70例正常人对照组之间基因型、等位基因频率的差异。结果:哮喘组和对照组IL-4受体基因Arg551Gln位点和IL-13基因Arg130Gln位点的基因型和等位基因型频率的差异有统计学意义,ADAM33基因T1位点基因型哮喘组和对照组差异有统计学意义,等位基因型频率在哮喘组和对照组差异无统计学意义。结论:提示IL-4R Arg551Gln(rs1801275)位和IL-13基因Arg130Gln(rs20541)位的多态性可能与中国皖南地区汉族哮喘有相关性;ADAM33基因(rs2280091)T1位点位的多态性可能与中国皖南地区汉族哮喘无相关性。     

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。     

中国汉族人群白细胞介素10启动子区基因多态性的等位基因频率

目的：了解中国汉族人群中白细胞介素10（IL-10）启动子区基因多态性的等位基因频率。方法：应用聚合酶链-限制性片段长度多态性分析（PCR—RFLP）技术,对131例健康中国汉族受检样本进行IL-10592、819、-1082三个位点的基因型检测。结果：IL-10-592位点A／A、C／A、C／C基因型频率分别为42．7％、36．6％、20．7％,IL-10 -819位点T／T、T／C、C／C基因型频率分别为42．7％、36．6％、20．7%;其相关等位基因频率与意大利高加索人及英国曼彻斯特人相比有显著性差异,但与韩国人之间的差异无统计学意义。结论：不同国家人群间存在IL-10启动子区基因多态性的差异。     

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。     

TLR7基因单核苷酸多态性与江苏淮安哮喘患者易感性的相关性研究

目的:探讨Toll样受体7(TLR7)基因rs179009、rs179019、rs5935436位点多态性与江苏淮安地区汉族人群支气管哮喘的相关性。方法:采用病例对照方法,以聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法比较158例支气管哮喘组与137例健康对照组之间基因型、等位基因频率的差异。结果:哮喘组TLR7基因rs179009、rs170019位点基因型及等位基因型频率与对照组相比差异有统计学意义(P<0.05)。rs5935436位点基因型及等位基因型频率在哮喘组和对照组间差异均无统计学意义(P>0.05)。结论:TLR7基因rs179009位点和rs179019位点的多态性可能与江苏淮安地区汉族人群哮喘相关;而rs5935436位点的多态性可能与江苏淮安地区汉族人群哮喘无关。     

IL-10基因启动子-592(C/A)多态性与血脂异常的关系

目的探讨川南地区汉族人IL-10基因启动子-592C/A(rs1800872)位点多态性与血脂异常的关系。方法应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法结合DNA测序法对425例样本进行IL-10-592C/A的基因多态性分析,其中血脂异常患者219例,对照样本206例。比较2组间基因型和基因频率的差异,并分析血脂异常组TC、TG、HDL-C和LDL-C 4项指标与基因型的关系。结果 IL-10-592C/A基因频率在血脂异常组和对照组分布无差异(P0.05),基因型(AA、AC、CC)分布结果具有统计学差异(P=0.026),且HDL-C异常组基因型分布与对照组比较差异显著(P=0.044),同时AA和AC基因型相对于CC基因型发生血脂异常和HDL-C异常的风险增加(OR1)。血脂异常组TC、TG、HDL-C和LDL-C 4项指标的血清水平在不同基因型间均未见差异(P0.05)。结论 IL-10-592C/A的基因多态性与川南地区汉人血脂异常尤其是HDL-C异常的发生相关,相对于基因型AA和AC,CC基因型是血脂异常的保护因素。     

Interleukin-18基因启动子区单核苷酸多态性与肝细胞癌遗传易感性关系的研究

目的探讨白细胞介素18(IL-18)基因启动子区-607C/A(rs1946518)和-137G/C(rs187238)单核苷酸多态性(SNP)与肝细胞癌(肝癌)遗传易感性的关系。方法应用序列特异性引物-聚合酶链反应(PCR-SSP)技术,检测228例肝癌患者和300例健康对照者IL-18基因启动子-607C/A(rs1946518)、-137G/C(rs187238)单核苷酸多态性位点基因型,分析肝癌患者和对照组基因型频率和等位基因频率分布。结果肝癌组SNP位点rs187238 G等位基因的频率明显高于对照组(OR=1.1891,95%CI=1.0106-1.5633,P=0.026)。携带rs187238 GG基因型的肝癌患者较多(OR=1.5168,95%CI=1.1490-1.8322,P=0.010)。分层分析发现,rs1946518位点上AA基因型与肝癌发病的关联在饮酒的肝癌患者中更加显著(P=0.024),而且rs187238位点上GC/CC基因型与肝癌发病的关联在出现肝癌复发的患者中更加显著(P=0.005)。结论 IL-18基因启动子区-137G/C(rs187238)GG基因型与肝癌遗传易感性有关联。而rs1946518位点AA基因型和rs187238位点GC/CC基因型分别与肝癌患者饮酒和肝癌复发有关联。     

Association between interleukin-10 gene promoter polymorphisms and susceptibility to liver cirrhosis

We conducted a case-control study to investigate the association between three common SNPs in IL-10 gene (rs1800896, rs1800871 and rs1800872) and the development of liver cirrhosis in a Chinese population. Between January 2013 and December 2014, a total of 318 patients with liver cirrhosis and 318 health control subjects were enrolled into our study. The IL-10 rs1800896, rs1800871 and rs1800872 polymorphisms were analyzed using polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By multivariate logistic regression analysis, we found that individuals with the AA genotype and GA+AA genotype of IL-10 rs1800896 were more likely to have an increased risk of liver cirrhosis when compared with the GG genotype, and the ORs (95% CI) for the AA genotype and GA+AA genotype were 2.04 (1.20-3.50) and 1.41 (1.02-1.96), respectively. We found that the GA+AA genotype of IL-10 rs1800896 had higher risk of liver cirrhosis in individuals with chronic hepatitis B when compared with the GG genotype (OR = 1.95, 95% CI = 1.01-3.59). In conclusion, we found that IL-10 rs1800896 polymorphism was correlated with an increased risk of liver cirrhosis, especially in individuals with chronic hepatitis B.     

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.     

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.     

The effect of IL-10 genetic variation and interleukin 10 serum levels on Crohn's disease susceptibility in a New Zealand population

Interleukin (IL)-10 has important effects in immunoregulation and inflammation, and previous studies have provided evidence for the involvement of IL-10 in the pathogenesis of Crohn's disease (CD). In this study, we investigated whether genetic variants of the IL-10 gene were associated with CD in a New Zealand population. Three single nucleotide polymorphisms (SNPs) in the promoter region of IL-10 (rs1800871, rs1800872, and rs1800896) and a flanking SNP, rs3024505, were genotyped in a well-characterized New Zealand dataset consisting of 342 CD cases and 610 controls. Furthermore, we measured serum IL-10 levels in a number of the CD patients and controls and examined whether a relationship existed between these polymorphisms and serum IL-10 levels. We demonstrated an association with CD for SNPs rs3024505 and rs1800896, and phenotypic analysis indicated an association of rs3024505 with an early age at first diagnosis, stricturing CD behavior, and requirement for bowel resection. We also observed that IL-10 concentration was significantly higher in CD patients than in the controls and that the T allele of rs1800896, the A allele of rs1800871, and the T allele of rs1800872 were associated with increased serum IL-10 levels.     

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).     

Polymorphisms in IL10 are associated with total Immunoglobulin E levels and Schistosoma mansoni infection intensity in a Brazilian population

Interleukin (IL)-10 is a regulatory cytokine of the helper T cell type 2 (TH2) pathway, which underlies both the host defense to helminthic infection and atopic diseases, including asthma. Although IL10 promoter polymorphisms are associated with increased atopy risk, IL10 variation has not been thoroughly explored in schistosomiasis-endemic populations. Three atopy-related IL10 promoter polymorphisms (rs1800896, rs1800871 and rs1800872), complemented by six tagging single-nucleotide polymorphisms (SNPs), were genotyped in 812 individuals in 318 nuclear families from a schistosomiasis-endemic area in Brazil. Associations between markers and total serum Immunoglobulin E (tIgE) levels, indicating non-specific activation of the TH2 pathway, and Schistosoma mansoni fecal egg counts, indicating burden of infection reflecting effectiveness of schistosomiasis host immunity, were performed using family-based transmission disequilibrium tests for quantitative traits (QTDTs). Alleles A, T and A at the three promoter SNPs rs1800896, rs1800871 and rs1800872 were associated with high tIgE levels in the same direction as in atopy populations (P=0.0008, 0.026 and 0.045), but not with egg counts. IL10 promoter polymorphisms appear to influence non-specific tIgE levels, but not schistosomiasis-specific immunity. The tagging SNP rs3024495 was associated with high S. mansoni egg counts (P=0.005), suggesting a novel locus in IL10 may influence clinically relevant burden of infection.     

白细胞介素27基因多态性与中国东北地区汉族人群支气管哮喘的相关性研究

目的:探讨东北地区汉族人群IL-27p28基因多态性与支气管哮喘易感性的关系。方法:采用聚合酶链式反应PCR技术和直接测序法,在200例支气管哮喘患者和111例健康对照者的IL-27p28启动子区g.-964A/G,外显子区g.2905T/G、g.4730T/C进行基因型检测,并对比分析出两组人群的基因型频率和等位基因频率的差异。结果:病例组和对照组的基因型分布均符合Hardy-weinberg平衡定律(P>0.05)。所检测三个位点的基因型频率及等位基因频率在病例组和对照组间的差异均无统计学意义(P>0.05)。结论:IL-27p28基因启动子区和外显子区单核苷酸多态g.-964A/G和g.2905T/G、g.4730T/C均未发现与中国东北地区汉族人群支气管哮喘易感性有显著相关。     

白介素13基因多态性与湖北汉族人群哮喘的关系

目的：为了探讨IL-13基因编码区精氨酸(Arg)110谷氨酰胺(Gln)多态性是否与湖北地区汉族人群哮喘及血浆总IgE水平升高相关。方法：采用PCR-RFLP方法，检测湖北地区43名哮喘患儿、45名成人哮喘患者、31名非哮喘儿童和46名体检健康成人的IL-13外显子4Arg110Gln的等位基因频率和基因型频率。用化学发光法测定血浆总IgE。结果：IL-13基因4257应等位基因a在儿童、成人中的频率分别为0．39、0．32。IL-13基因Arg110Gln多态性的GlnGln型与儿童哮喘和血浆总IgE升高相关(P分别为0．030、0．0009)，但与成人哮喘、血浆总IgE水平之间无统计学意义(P分别为0．219、0．174)。结论：研究显示IL-13外显子4Arg110Gln g/a单核苷酸多态性与湖北汉族儿童哮喘和血浆总ISE水平相关，但与成人哮喘、血浆总IgE水平之间无统计学意义。