2型糖尿病与白细胞介素-10及其基因多态性的关系

<正>糖尿病前期患病率约为24.5%〔1〕。同时糖尿病又可增加严重的老年性疾病风险,比如糖尿病能够增加卒中风险2⁵倍〔2〕,而2型糖尿病(T2DM)患者血糖波动也可以增加动脉粥样硬化斑块风险〔3〕。T2DM发病机制尚未完全阐明,近年来研究认为T2DM可能是细胞因子介导的炎症反应,炎症在糖尿病的发病机制中起媒介作用。血浆中白细胞介素(IL)-10主要来自Th2细胞的分泌,它参与机体的慢性炎性反应,同时以不同     

白细胞介素-10与癫痫关系的研究进展

从白细胞介素-10(IL-10)的生物学特性、癫痫发病时脑内IL-10的变化及IL-10在癫痫脑损伤中的作用等方面进行综述,免疫手段有望成为治疗癫痫的一个新视窗.     

白细胞介素-10基因多态性与乙型肝炎病毒感染的关系

目的:探讨中国人白细胞介素-10基因启动子单核苷酸多态性与乙型肝炎病毒感染之后临床发展之间的关系.方法:分别采用聚合酶链反应-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478例慢性乙型肝炎患者,223例乙肝病毒携带者及267例自限性感染者基因组DNAIL-10基因启动子区域3个多态位点-592、-819、-1082的基因多态性,并进行相关性分析.结果:IL-10-1082A等位基因及AA基因型在慢性乙型肝炎患者组的频率明显高于自限性感染者组和乙肝病毒携带者组(A:χ2=37.72,P=0.000;χ2=45.23,P=0.000;AA:χ2=20.53,P=0.000;χ2=19.14,P=0.000).IL-10-819T等位基因及TT基因型在慢性乙型肝炎患者组的频率也高于自限性感染者组和乙肝病毒携带者组(T:χ2=10.5,P<0.001;χ2=17.38,P<0.001;TT:χ2=8.76,P=0.003;χ2=5.656,P=0.017).IL-10-592C/A等位基因频率和AA/CC/AC基因型在三组的分布没有统计学意义(P>0.05).结论:IL-10基因启动子多态性与乙肝病毒感染后临床发展过程可能相关.     

白细胞介素-10基因多态性与自身免疫性肝病相关性研究

目的研究白细胞介素10(IL-10)基因启动子区域-592、-819和-1082位单核昔酸多态性与自身免疫性肝病发病之间的关系。方法分别采用聚合酶链反应限制性片段长度多态性分析法(PCRRFLP)和聚合酶链反应一序列特异性引物扩增法(PCRSSP)检测54例自身免疫性肝炎(AIH)，77例原发性胆汁性肝硬化(PBC)患者及160例健康献血员外周血单个核细胞基因组DNA IL-10基因启动子区域3个多态位点-592，-819、-1082的基因多态性，并进行相关性分析。结果54例AIH和77例PBC患者与160例健康对照组的IL-10启动子-1082、-819和592基因型分布的统计学分析表明，差异无显著性。结论IL-10启动子基因多态性与自身免疫性肝病发病之间无显著关联性。     

白细胞介素-10对骨质疏松小鼠牙槽骨吸收的保护作用

目的观察白细胞介素(IL)-10对骨质疏松(OP)小鼠牙槽骨的影响,探究其对牙槽骨吸收的保护作用。方法用雌性小鼠构建OP模型小鼠后随机分为空白组、模型组,高、中、低剂量IL-10组。各组尾静脉注射分别给予生理盐水和IL-10,2次/w。给药4 w后处死小鼠,分别取下颌骨和静脉血。下颌骨常规脱钙,石蜡包埋、切片、HE染色,观察下颌骨变化。静脉血用于分离血清检测IL-1β水平。结果与空白组相比,模型组骨破坏严重。与模型组相比,IL-10高、中、低剂量组骨密度显著增高,骨质破坏缓解。血清中IL-1β含量明显下降,其中以中、高剂量组为最好。结论IL-10对OP小鼠牙槽骨吸收有保护作用,且该作用与抑制炎症过程有关。     

白细胞介素10基因多态性与脑梗死的关系

目的探讨白细胞介素10（IL-10）基因多态性与脑梗死的关系。方法用聚合酶链反应一限制性片段长度多态性技术，对204例脑梗死患者（脑梗死组）和131名健康者（对照组）的IL-10-592C／A、IL-10-819C／T及IL-10．1082G／A，共3个位点的基因多态性进行分析。结果脑梗死组IL-10—1082G／A基因型的分布频率与对照组比较，差异有统计学意义（X^2=11．764，P=0．001）；IL-10-1082A等位基因频率为99．5％，对照组为95．8％，两组比较差异有统计学意义（P=0．001）；IL-10-592C／A和IL-10-819C／T的基因型分布频率及等位基因频率与对照组比较差异无统计学意义（P〉0．05）。结论IL-10—1082G／A基因多态性与脑梗死的发病有一定关系，其中A等位基因频率增高与脑梗死发病有关。     

白细胞介素-10受体1基因多态性与系统性红斑狼疮ds-DNA抗体水平关系的研究

系统性红斑狼疮(SLE)是一种病因尚未完全明了的自体免疫性疾病,其特征性表现为针对自身核蛋白的高滴度抗体形成,严重时会形成免疫复合物沉积在基底膜上,导致肾小球肾炎和终末期肾衰竭.免疫异常是本病发生的关键,涉及T、B淋巴细胞、单核、自然杀伤(NK)细胞等几乎所有单个核细胞及众多细胞因子网络.其中血清白细胞介素-10(IL-10)浓度和分泌细胞数量与SLE发病相关,且与启动子区的多态性有关,然而在人类尚未发现与炎症反应直接相关的IL-10通路异常.     

白细胞介素-18与糖尿病及其并发症的关系

近年来的研究表明,白细胞介素-18(IL-18)作为一种前炎症细胞因子,通过促发炎症因子生成,导致Th1/Th2细胞因子失平衡及胰岛β细胞凋亡而与糖尿病的发生、发展相联系,并且通过多种机制影响糖尿病的大血管病变和微血管病变(主要为糖尿病肾病和糖尿病视网膜病)的发生.同时,IL-18的基因多态性也是糖尿病研究领域中一个倍受关注的焦点.     

白细胞介素-10与急性脑血管病

白细胞介素 10 (IL 10 )由单核巨噬细胞、淋巴细胞等产生的是多向性生物活性的免疫抑制因子 ,具有抗炎作用 ,能抑制动脉粥样硬化斑块的形成。随着人们对脑血管病发病机制中免疫反应及炎症因素作用的进一步认识 ,使IL 10对脑血管病的治疗具有潜在的应用前景。文章介绍了IL 10的生物学特性、在急性脑血管病中的作用机制和神经保护作用     

白细胞介素10与动脉粥样硬化

炎症是动脉粥样硬化 (AS)发生发展的重要环节 ,包括炎性细胞浸润 ,大量的炎症因子表达 ,以及各种炎症因子参与调节的细胞增殖、凋亡 ,细胞外基质重排以及血管重塑。除致炎因子外 ,抗炎因子如白细胞介素10 (IL- 10 )也在 AS斑块中呈现表达拮抗炎性因子的作用 ,成为机体代偿性保护机制之一。1　白细胞介素 10六十年代 ,Mosmann等根据细胞因子的优势分泌效应 ,提出存在二类 T辅助细胞 (TH1和 TH2 )的假说 ,即 TH1细胞分泌 IL - 2 ,IFN-γ,主要诱导巨噬细胞活化和介导迟发型变态反应 ,TH2主要分泌 IL- 4、IL- 5 ,主要介导体液免疫应答…     

白细胞介素10基因启动子-1082A/G及-819T/C多态性与早发冠心病的相关性

目的探讨白细胞介素10(IL-10)基因启动子-1082A/G、-819T/C多态性与中国早发冠心病的相关性。方法早发冠心病(病例组)92例,对照组94例,采用苯酚-氯仿法提取DNA,聚合酶链反应-限制性片段长度多态性方法(PCR-RFLP)分析IL-10基因启动子-1082A/G、-819T/C多态性。结果病例组与对照组IL-10-1082A/G,AA、AG、GG基因型频率及A、G等位基因频率差异均无统计学意义(均P>0·05);IL-10-819T/C,TT、TC、CC基因型频率及T、C等位基因频率差异亦均无统计学意义(均P>0·05)。结论IL-10基因启动子-1082A/G和-819T/C多态性可能与中国早发冠心病的易感性无关。     

The association between rs1800872 polymorphism in interleukin-10 and risk of cervical cancer: A meta-analysis

Background:In recent years, several reports have tried to prove this connection between rs1800872 polymorphism in interleukin-10 and cervical cancer among different populations, but the results are debatable. Thus, we collected all the published literature and conducted an integrated meta-analysis, which provided better evidence-based medicine for the relationship between rs1800872 polymorphism in interleukin-10 and risk of cervical cancer.Methods:We systematically performed our search on PubMed, EMBASE, Web of Science, WanFang database, and CNKI for all papers related to this research, published up to August 1, 2020. Summary odds ratios (OR) with 95% confidence interval (95% CI) were calculated in allelic, homozygous, heterozygous, dominant, and recessive model to appraise the association.Results:The meta-analysis included 8 studies containing 1393 cervical cancer cases and 1307 controls. The aggregate data under heterozygous model and dominant inheritance model (OR = 0.66, 95% CI: 0.55--0.80) indicated a significant association between rs1800872 and the low risk of cervical cancer in the entire population. And the aggregated data under the dominant inheritance model shows that rs1800872 is significantly associated with the reduction in the risk of cervical tumors in the entire population.Conclusion:Our conclusion is that the AC/AA + AC variant of Rs1800872 indicates a protective effect in the development of cervical cancer.     

Association of interleukin-10 polymorphisms with risk of irritable bowel syndrome:A meta-analysis

AIM:To clarify the current understanding of the association between interleukin-10(IL-10)polymorphisms and the risk of irritable bowel syndrome(IBS).METHODS:We searched for studies in any language recorded in PubMed,Embase and Cochrane library before August 2013.The associations under allele contrast model,codominant model,dominant model,and recessive model were analyzed.The strengths of the association between IL-10 polymorphisms and IBS risk were estimated using odds ratios(OR)with 95%confidence interval(CI).Fixed effects model was used to pool the result if the test of heterogeneity was not significant,otherwise the random-effect model was selected.RESULTS:Eight case-control studies analyzing three single-nucleotide polymorphisms rs1800870(-1082 A/G),rs1800871(-819C/T),and rs1800872(-592A/C)of the IL-10 gene,which involved 928 cases and 1363 controls,were eligible for our analysis.The results showed that rs1800870 polymorphisms were associated with a decreased risk of IBS(GG+GA vs AA:OR=0.80,95%CI:0.66-0.96),(AA+GA vs GG:OR=0.68,95%CI:0.52-0.90).Subgroup analysis revealed such association only existed in Caucasian ethnicity(AA+GA vs GG,OR=0.70,95%CI:0.55-0.89).The rs1800872 polymorphisms were associated with an increased risk of IBS in Asian ethnicity(CC vs GG:OR=1.29,95%CI:1.01-1.16).There were no associations between rs1800871 polymorphisms and the IBS risk.CONCLUSION:The results suggest that IL-10 rs1800870confers susceptibility to the risk of IBS in Caucasian ethnicity,and the rs1800872 may associate with IBS risk in Asians.However,no significant associations are found between rs1800871 and IBS risk.     

白细胞介素1基因多态性与北京地区胃癌的关系

目的　了解白细胞介素 (IL) 1β 31、IL 1β 5 11和IL 1受体拮抗因子基因 (IL 1RN)多态性在北京地区胃癌患者及慢性胃炎患者中的分布情况 ,探讨IL 1基因多态性与北京地区胃癌的关系。方法　收集北京地区 5 7例胃癌患者和 12 0例慢性胃炎患者的外周血标本 ,提取DNA ,用聚合酶链反应 限制性片段长度多态性法 (PCR RFLP)检测入选患者的IL 1基因多态性情况 ,并比较这些基因多态性在胃癌组和慢性胃炎组的分布差异。结果　IL 1β 31C等位基因在慢性胃炎组和胃癌组中的分布频率分别为 4 9.2 %和 6 1.4 % ,胃癌组明显高于慢性胃炎组 (P <0 .0 5 ) ,携带IL 1β 31C等位基因增加胃癌的风险性 ,IL 1β 31C/C纯合子型的胃癌风险OR值为 2 .4 (95 %CI =1.0～ 5 .9)。IL 1β 5 11T等位基因在慢性胃炎组和胃癌组中的分布频率分别为 4 7.9%和 6 5 .8% ,胃癌组明显高于慢性胃炎组 (P <0 .0 1) ,携带IL 1β 5 11T等位基因增加胃癌的风险性 ,IL 1β 5 11T/T纯合子型的胃癌风险OR值为 3.8(95 %CI =1.5～ 9.7)。IL 1RN 2等位基因在慢性胃炎组和胃癌组中的分布频率分别为 3.8%和 11.4 % ,胃癌组明显高于慢性胃炎组 (P <0 .0 1) ,携带IL 1RN 2等位基因增加胃癌的风险性 ,L/ 2杂合子型的胃癌风险OR值为 3.5 (95 %CI =1.4～ 8.9     

人白细胞介素-1受体拮抗剂或白细胞介素-10逆转录病毒载体的构建与体外实验

目的 构建携带人白细胞介素-1受体拮抗剂(hIL-1Ra)或人白细胞介素-10(hIL-10)基因的重组逆转录病毒(rRv)，体外转染免滑膜成纤维样细胞，检测目的基因的表达水平与持续时间。方法 提取人外周血单个核细胞总RNA，反转录聚合酶链反应(RT-PCR)扩增目的基因；酶切、连接目的基因与逆转录病毒载体pLXSN，筛出阳性克隆，经GP2-293细胞包装，收集病毒并鉴定；rRV-hlL-1Ra、rRV-hlI-10分别体外转染兔滑膜成纤维样细胞，RT-PcR测定目的基因mRNA表达水平与时间的关系。免疫组织化学与免疫印迹测定蛋白水平的表达与持续时间。结果 成功构建了携带hIL-1Ra或hIL-10基因的重组逆转录病毒，rRv-hIL-1Ra与rRV-hIL-10均能有效转染体外培养的兔滑膜成纤维样细胞，RT-PcR测定目的基因mRNA高峰均出现于转染后第5天左右。免疫组织化学和免疫印迹均检测到hIL-lRa、hlL-10的表达。经G418筛选后的细胞中，hIL-1Ra的表达在转染后第30天内达高峰，至少持续60d：hIL-10的表达至少持续40d。结论 以重组逆转录病毒为载体可以成功地将hIL-lRa或hIL-10基因导人体外培养的兔滑膜成纤维样细胞并实现稳定表达。     

白细胞介素-10和肿瘤坏死因子基因多态性与湖北汉族人群胃十二指肠疾病及幽门螺杆菌感染的相关性

目的 研究我同湖北汉族人群IL-10及TNF的基因多态性与胃十二指肠疾病及幽门螺杆菌(Hp)感染的关系.方法 采用病例财照研究和聚合酶链反应.限制性片段长度多态性(PCR-RFLP)方法检测605例胃十二指肠疾病患者(包括196例慢性胃炎、189例胃十二指肠溃疡及220例胃癌患者)和624例健康对照者中IL-10基因启动子区3个位点(IL-10-1082/-819/-592)的等位基因型和TNFα-308、LTα(淋巴毒素α,亦称TNFβ)Nco Ⅰ、AspH Ⅰ双等位基因型分布;用ELISA法检测血清中Hp-IgG及cagA-IgG抗体水平.结果 (1)IL-10-1082 AG+GG基因型在胃癌组、慢性胃炎组及胃十二指肠溃疡组(非胃癌组)、健康对照组分布频率分别为20.0%、7.5%、6.0%和5.0%,IL-10-1082 AG+GG基因型分布在非胃痛组及健康对照组之间差异无统计学意义(P>0.05),而胃癌组高于非胃癌组(P<0.05)及健康对照组(P<0.05),其差异均有统计学意义.胃癌组中IL-10-592及-819两个位点与非胃癌组及健康对照组比较,基因型分布差异无统计学意义(P>0.05).IL-10-819位点与IL-10-592位点基因型分布频率一致.(2)胃癌组与其余3组比较,IL-10-1082 AG+GG基因型且Hp阳性的分布频率的差异有统计学意义(P<0.05).(3)LTα Nco Ⅰ AG基因型在Hp阳性胃癌患者中(66.7%)高于Hp阳性的健康对照组(47.8%),差异有统计学意义(P<0.05),该基因型与其他胃十二指肠疾病尤相关性.TNFα-308、LTα AspH Ⅰ与Hp感染及胃十二指肠疾病亦无相关性.结论 (1)IL-10-1082 AG+GG基因型与湖北地区汉族人群胃癌发生有相关性.(2)IL-10-1082 AG+GG基因型和LTα Nco Ⅰ AG基因型与湖北汉族人群Hp阳性胃癌有相关性.     

Comparison of single nucleotide polymorphisms in the human interleukin-10 gene promoter between rheumatoid arthritis patients and normal subjects in Malaysia

In this study, three single nucleotide polymorphisms (SNPs) located within the promoter of the human interleukin (IL)-10 gene [rs1800896 (position: −1087G > A), rs1800871 (position: −824C > T) and rs1800872 (position: −597C > A)] were investigated in 84 rheumatoid arthritis (RA) patients and 95 age- and sex-matched healthy subjects using polymerase chain reaction-restriction fragment length polymorphism method. Production of IL-10 by peripheral blood lymphocytes from the RA patients and healthy subjects cultured in the presence of Concanavalin A (Con A) was determined by using enzyme-linked immunosorbent assay. The results show that the distribution of the IL-10 genotypes did not differ significantly between RA patients and healthy subjects (P > 0.05). However, a significant difference was observed in allele frequencies of −824CT, −824TT, −597CA, and −597AA between the RA patients and healthy volunteers (P = 0.04). The −1087A/−824T/−597A (ATA) haplotype, which comprises all mutant alleles, was associated with lower IL-10 production when compared with the other haplotypes. In contrast, the RA patients who did not display the ATA haplotype produced significantly higher levels of IL-10 when compared with those carrying either one (P = 0.012) or two (P = 0.005) ATA haplotypes. Our findings suggest that there is an association between SNPs in the promoter of the human IL-10 gene and susceptibility to RA. An erratum to this article is available at .     

Comparison of single nucleotide polymorphisms in the human interleukin-10 gene promoter between rheumatoid arthritis patients and normal subjects in Malaysia

Abstract

In this study, three single nucleotide polymorphisms (SNPs) located within the promoter of the human interleukin (IL)-10 gene [rs1800896 (position: ?1087G > A), rs1800871 (position: ?824C > T) and rs1800872 (position: ?597C > A)] were investigated in 84 rheumatoid arthritis (RA) patients and 95 age- and sex-matched healthy subjects using polymerase chain reaction-restriction fragment length polymorphism method. Production of IL-10 by peripheral blood lymphocytes from the RA patients and healthy subjects cultured in the presence of Concanavalin A (Con A) was determined by using enzyme-linked immunosorbent assay. The results show that the distribution of the IL-10 genotypes did not differ significantly between RA patients and healthy subjects (P > 0.05). However, a significant difference was observed in allele frequencies of ?824CT, ?824TT, ?597CA, and ?597AA between the RA patients and healthy volunteers (P = 0.04). The ?1087A/?824T/?597A (ATA) haplotype, which comprises all mutant alleles, was associated with lower IL-10 production when compared with the other haplotypes. In contrast, the RA patients who did not display the ATA haplotype produced significantly higher levels of IL-10 when compared with those carrying either one (P = 0.012) or two (P = 0.005) ATA haplotypes. Our findings suggest that there is an association between SNPs in the promoter of the human IL-10 gene and susceptibility to RA.