KHSRP基因多态性与家族性热性惊厥关联研究

目的 研究KH型剪切调控蛋白（KH-type splicing regulatory protein,KHSRP)基因的单核苷酸多态性（single nucleotide polymorphisms,SNPs)与家族性热性惊厥（febrile convulsions,FC)的关系。方法 通过NCBI的dbSNP数据库搜索KHSRP基因的单核苷酸多态性位点，运用位点特异性PCR（site-specificPCR amplification,SSP)和变性高效液相色谱（Dena-turing High Performance Liquid Chromatography,DHPLC)技术对来自中国北方的健康人群和家族性惊厥病人进行SNPs基因分型。结果 KHSRP基因三个多态性住点的基因型在健康人群均符合 Hardy-Weinberg平衡，各等位基因频率和基因型频率在病人和健康人无显著差异。结论 KHSRP基因的3个多态性位点的SNPs均与FC不相关，提示KHSRP基因可能不是FC的易感基因。     

家族性热性惊厥患儿酪蛋白激酶γ2基因单核苷酸多态性研究

目的　研究酪蛋白激酶γ2 (caseinkinaseⅠ gamma 2 ,CSNK1G2 )基因单核苷酸多态性 (singlenucleotidepolymorphisms ,SNPs)位点与家族性热性惊厥的关系。 方法　通过NCBI的dbSNP数据库选择CSNK1G2基因的 5个单核苷酸多态性位点 ,应用聚合酶链式反应 限制性内切酶片段长度多态性技术 ,检测 5 3例家族性热性惊厥患儿和 10 1名健康对照者的CSNK1G2基因 5个SNPs位点的基因型 ,并使用EH1.2 0程序构建单体型并以单体型为标记进行进一步的患儿和正常人相关分析。结果　 5个SNPs位点的基因型频率在惊厥患儿和正常人群中分布均符合Hardy Weinberg平衡。其中 3个位点SNPrs740 42 3、rs2 2 7773 7、rs10 5 9684的基因型频率和基因频率在家族性热性惊厥患儿和对照组分布差异有显著性 (P <0 .0 5 ) ,1个位点rs2 0 74882基因型频率和基因频率在两组人群中分布差异无显著性 (P >0 .0 5 ) ,另一位点rs480 682 5因基因频率较低 ,故未作统计。结论　CSNK1G2基因SNPsrs740 42 3、rs2 2 7773 7、rs10 5 9684可能与家族性热性惊厥相关。     

家族性热性惊厥相关基因研究进展

热性惊厥是小儿时基因体温升高诱发的一种特殊的癫痫综合征，多数病儿呈良性经过，少数可转为癫痫，近年来越来越多的研究表明，热性惊厥有明显的遗传倾向，国内外对ＦＣ进行了大量遗传学研究和相关基因染色体定位工作，本就该领域的进展进行综述。     

小儿热性惊厥的脑电图

本文对296例小儿热性惊厥脑电图进行分析。结果:小儿热性惊厥脑电图(EEG)异常率48.65％,主要以阵性高幅慢波为主(77.78％)。小儿癫痫脑电图异常率(89.61％)。主要以阵发性棘慢波和局灶性改变为主(62.78％)。二周后EEG复查热性惊厥EEG大部分恢复正常(83.35％)。而小儿癫痫EEG未有恢复正常的。热性惊厥发作次数愈多,发作持续时间愈长EEG改变愈明显,二周后脑电图恢复正常的愈少。这对小儿热性惊厥的诊断和预后判定有重要价值。     

家族性热性惊厥与CAPS基因的相关分析

目的研究CAPS(calcyphsine)基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点与家族性热性惊厥(febrile seizures,FS)的关系.方法通过NCBI的dbSNP数据库选择CAPS基因的2个单核苷酸多态性位点,应用聚合酶链式反应-限制性内切酶长度多态性技术,检测54例家族性热性惊厥患儿和90名健康对照者的CAPS基因2个SNPs位点的基因型,用SPSS软件判定个单核苷酸多态性基因型频率分布是否符合Hardy-Weinberg平衡,SNPs基因型频率和基因频率在正常人和患儿中的分布比较用R×C和2×2表x2检验并经连续性校正.结果位点rs7249419的基因型频率符合Hardy-Weinberg平衡,但是它的最小等位基因频率不足1%,其基因型频率和等位基因频率在正常人和患儿间的分布无显著性差异(P＞0.05).位点rs11437855只有1种基因型,均为无插入的纯合子.结论CAPS基因SNP rs7249419、rs11437855可能与家族性热性惊厥无关.     

家族性热性惊厥相关基因研究进展

热性惊厥（ｆｅｂｒｉｌｅ ｃｏｎｖｕｌｓｉｏｎｓ,ＦＣ）是小儿时期因体温升高诱发的一种特殊的癫痫综合征,多数病儿呈良性经过,少数可转为癫痫。近年来越来越多的研究表明,热性惊厥有明显的遗传倾向,国内外对ＦＣ进行了大量遗传学研究和相关基因染色体定位工作,本文就该领域的最新进展进行综述。     

家族性热性惊厥遗传特点分析

家族性热性惊厥遗传特点分析戚豫张建慧林庆邹丽萍吴希如热性惊厥（ｆｅｂｒｉｌｅｃｏｎｖｕｌｓｉｏｎｓ，ＦＣ）是小儿常见病，发病率为５％～６％，有明显的遗传倾向［１，２］，但其遗传方式尚无定论。曾有常染色体隐性遗传、多基因遗传和母系遗传等多种说法，近来倾...     

STK11基因多态性与家族性热性惊厥关联研究

目的研究丝氨酸/苏氨酸蛋白激酶11(serine/threonine kinase 11,STK11)基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点与家族性热性惊厥(familial febrile convulsions,FC)的关系.方法用关联分析的方法,结合传递不平衡检验(transmission disequilibrium test,TDT),对来自中国北方的家族性热性惊厥病人和对照组进行分析.结果 SNPs位点的基因型频率在惊厥患儿和对照组中分布均符合Hardy-Weinberg平衡.前期实验位点rs741764的基因型频率和基因频率及rs2075604的基因型频率在两组人群中分布差异有显著性(P＜0.05),后期选择一般人群作为对照组进行的关联分析,除rs741764基因型频率在两组间差异有显著性(P＜0.05)外,其余差异均无显著性.进一步用TDT得到3个位点都没有发现传递不平衡现象.结论 STK11基因的四个SNPs位点均与家族性热性惊厥不相关,STK11基因可能不是中国北方人家族性热性惊厥的易感基因.     

小儿热性惊厥与癫痈关系的脑电图分析

热性惊厥（FC）是小儿时期比较常见的一种急症，在部分患儿中可引起脑电图（EEG）不同程度的异常改变，脑电图检查在FC中的作用日益受到重视，并已作为FC的常规检查。我们对在2000～2003年在我科就治的51例FC患儿作了EEG检查。本文通过对这些患儿的EEG检查结果进行分析，探讨小儿FC对其脑功能的影响以及FC时EEG之表现与小儿年龄、发热程度、复发次数、以后癫痫发作的关系。现将结果报告如下。     

儿童热性惊厥脑电图改变

单纯性热性惊厥是指非中枢神经系统所致的发热T38℃以上,所引起的全身抽搐伴意识丧失数分钟而言,是小儿比较常见的一种急症,大多数发生于四个月至五岁以下的儿童,复杂性的热性惊厥儿童可大于六岁,绝大多数是由于上呼吸道感染引起发热,由于小儿神经系统发育不完善,体温中枢不稳定,对热阈值耐受性差而致抽搐,有家族史者复发率高。本文对115例热性惊厥患儿进行了脑电图观察,现将结果报告如下:     

新生儿全身炎症反应综合征与IL-10基因多态性的相关性研究

目的探讨IL-10基因启动子区1082位点基因型及等位基因与新生儿全身炎症反应综合征(SIRS)的关系。方法采用ELISA法检测血清IL-10水平及限制片断长度多态分析-聚合酶链反应方法(RFLP/PCR)对54例全身炎症反应综合征新生儿和40例随机挑选健康体检的新生儿的IL-10的基因启动子区1082位点等位基因进行分析,计算该位点的基因分布频率和相对危险度OR值;并进行卡方检验,筛选有意义基因型。结果(1)SIRS组血清IL-10水平显著升高,与对照组比较差异显著。(2)SIRS组患儿IL-10 1082位点GG型分布频率为61.1%,AA分布频率为5.6%,GA分布频率为33.3%,以上三个基因型在疾病组与正常组之间进行卡方检验,χ2值分别为7.53,1.30,6.00,GG型与正常对照组比较均有显著性差异(P<0.01)。AA型与正常对照组比较亦有显著性差异(P<0.05)。疾病组G等位基因的分布频率为77.8%;A等位基因的分布频率为22.2%;疾病组与正常组之间进行逐个基因型的比较,以相对危险度0R值计算,计算结果GG的0R值为3.26;AA的0R值为0.20;GA的0R值为0.61。结论IL-10的基因启动子区1082位点GG是中国北方汉族新生儿SIRS的易感基因;而AA为抗感基因。通过对IL-10基因启动子区1082位点的基因多态性的搜索,发现IL-10基因启动子区1082位点的基因型对新生儿SIRS的发生、发展、诊断、预后、预测有重要意义。     

白介素-10-627基因多态性和儿童哮喘的相关性研究

目的探讨白介素-10(IL-10)基因-627位点多态性与昆明地区儿童哮喘的相关性。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法,检测50例哮喘儿童和36例健康儿童IL-10基因-627位点基因型,比较两组IL-10基因-627位点的基因型和等位基因分布频率。结果哮喘组和健康组3种基因型CC、CA、AA分别为:12.0%、48.0%、40.0%;8.3%、50.0%、41.7%。两组基因型分布差异无显著性(P>0.05)。哮喘组和健康组C和A的等位基因分布频率分别为:36.0%、64.0%;31.9%、68.1%。两组等位基因分布频率差异无显著性(P>0.05)。结论本研究表明IL-10基因-627位点多态性可能与昆明地区儿童哮喘易感性无关。     

IL-10-592 polymorphism is associated with IL-10 expression and severity of enterovirus 71 infection in chinese children

BackgroundEnterovirus 71 (EV71) infection results in some severe complications with high mortality and disability in Hand, Foot and Mouth Disease (HFMD) in children. Recent studies have shown that cytokine genetic predispositions have associations with both the development of EV71 infection and severity of HFMD.ObjectiveThis study was designed to investigate whether the IL-10–592 polymorphism is associated with IL-10 levels and disease severity in Chinese children with EV71 infection.Study designIn patients selected, there were 378 cases with EV71 infection (including 291 mild cases, 70 severe cases and 17 critical cases), as well as 406 health controls. EV71 in serum was tested by RT-PCR, and IL-10-592 genotype was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis techniques.ResultThe IL-10-592C allele was observed with higher frequency in patients with critical EV71 infection (70.59%) compared with severe EV71 infection (41.43%, P < 0.01), mild EV71 infection (43.81%, P < 0.01) and healthy children (44.46%, P < 0.01). The blood IL-10 levels of critical cases were significantly higher than severe cases, mild cases, and healthy children. Among all of the four groups, IL-10 levels in patients with genotype AA were significantly lower than those with genotypes AC + CC (t = 4.86, P < 0.05; t = 2.30, P < 0.05; t = 3.44, P < 0.05; t = 5.58, P < 0.05).ConclusionIL-10-592C allele is associated with IL-10 expressions and the severity of EV71 infection in Chinese patients.     

Differential production of IL-10 by T cells and monocytes of HIV-infected individuals: association of IL-10 production with CD28-mediated immune responsiveness

Immune unresponsiveness in HIV-1 infection can result from impaired signals delivered by the costimulatory CD28-B7 pathway and the altered production of immunoregulatory cytokines, in particular IL-10, whose production is altered in HIV-1 infection. In this study we investigate IL-10 regulation in T cells and monocytes from HIV⁺ individuals, and its association with CD28-mediated T cell proliferation. IL-10 production as analysed in T cell- and monocyte-depleted peripheral blood mononuclear cells (PBMC), and by intracellular staining at the single-cell level, reveals a defect in IL-10 production by CD4⁺ and CD8⁺ T cells, whereas monocytes constitute the major IL-10-producing cell type. To investigate the impact of IL-10 on immune responsiveness, CD28-mediated proliferative responses in HIV⁺ individuals were correlated with PHA-induced IL-10 production. CD4⁺ T cells expressed CD28, yet exhibited markedly reduced CD28-mediated cell proliferation. This CD28-mediated CD4⁺ T cell proliferation was found to be inversely associated with the levels of PHA-induced IL-10 production and could be restored, at least in part, by anti-IL-10 antibodies. These results suggest that IL-10 production is differentially regulated in T cells and monocytes of HIV⁺ individuals, and that IL-10 may have a role in inducing immune unresponsiveness by modulating the CD28-B7 pathway.     

谷氨酰胺、地塞米松对内毒素血症大鼠血清IL-8,IL-10的影响

目的通过观察谷氨酰胺、地塞米松对内毒素血症大鼠血清IL-8,IL-10的影响,探讨地塞米松、谷氨酰胺对内毒素血症大鼠的保护途径.方法选健康18日龄Wistar大鼠120只,随机取8只腹腔注射生理盐水作对照组(0h),余大鼠按腹腔注射药物不同分成内毒素(L)、谷氨酰胺预防(Gln)地塞米松治疗(D1)组,每组40只,各组于加LPS后2、4、6、24及72h分别断头取血,用放免法测定IL-8,IL-10.结果(1)L组IL-8在2、24h出现两次升高,前者升高程度更明显,差异显著,P<0.01;D1和C1n组各时间点IL-8均低于L组,尤其以2h抑制作用更强,差异显著,P<0.01;Gln组第一次高峰在6h.(2)L组IL-10在2、72h出现两次升高,后者升高程度更明显,差异显著,P<0.01;D1和Gln组第二次升高均提前至24h,增幅最高的为D1组,而其它各时间点IL-10均以Gln组升高明显,差异显著,P<0.01.结论细胞因子IL-8/IL-10在内毒素血症中起主要的损害与抗损害作用,地塞米松治疗对机体能抑制损伤/促进修复;谷氨酰胺不仅有与地塞米松相似的作用,而且可使损伤延迟,二者都能使修复作用提前.     

子宫内膜异位症并不孕患者IL-10，IL13含量变化及其临床意义

目的检测IL-10和IL-13在子宫内膜异位症并不孕患者腹腔液及外周血中含量并探讨其意义。方法电视腹腔镜手术中采集EMS并不孕及对照组的腹腔液,术前空腹抽取外周血,采用ELISA法检测细胞因子水平。EMS并不孕组及对照组中,分别抽取38份腹腔液、外周血测IL-10及IL-13。结果EMS并不孕组和对照组腹腔液IL-10的含量分别为（15.8±12.9）pg/ml和（10.6±5.7）pg/ml,外周血中分别为（13.8±9.9）pg/ml和（8.6±5.7）pg/ml,两组比较均无统计学意义（P〉0.05）;EMS并不孕组和对照组腹腔液IL-13的含量分别为（93±9.6）pg/ml和（114±26）pg/ml,外周血中分别为（78±7.6）pg/ml和（102±29）pg/ml,两组比较均有统计学意义（P〈0.05）。结论异位子宫内膜细胞可抑制IL-13的产生,进而营造免疫抑制微环境,干扰免疫调节功能。     

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.     

孟鲁司特对支气管哮喘患者血清IL-6、IL-8和IL-10水平的影响

目的:探讨孟鲁司特在支气管哮喘患者体内IL-6、IL-8和IL-10水平的影响。方法:应用放射免疫分析和酶联法对31例支气管哮喘患者应用孟鲁司特治疗前后血清IL-6、IL-8和IL-10水平的变化,并与35名正常健康人作比较。结果:支气管哮喘患者在治疗前血清IL-6、IL-8水平非常显著地高于正常人组(P<0.01),而IL-10水平显著地低于正常人组(P<0.01),经治疗2周后与正常人组比较仍有显著性差异(P<0.05)。结论:孟鲁司特对支气管哮喘患者血清IL-6、IL-8和IL-10有一定程度的调节作用,从而降低患者体内的炎症水平,促进病情缓解和好转。     

IL-10对大鼠原代肝细胞增殖的影响

目的:探讨IL-10对体外培养大鼠原代肝细胞增殖的影响。方法:胶原蛋白酶原位灌流法分离大鼠肝细胞,RT-PCR法检测肝内不同细胞标志基因的表达情况,对比原代肝细胞与大鼠正常肝组织的检测结果,进行细胞纯度鉴定;RT-PCR法检测原代肝细胞IL-10和IL-10受体α(IL10Rα)的表达情况;原代肝细胞分3组培养:正常组(N组)、对照组(C组)和IL-10干预组(I组);通过MTT分析、台盼兰细胞计数以及流式细胞术检测DNA含量等方法,了解外源性IL-10对肝细胞增殖的影响。结果:细胞鉴定结果显示,所有的标志基因在肝组织都可检测到有较高的表达,原代肝细胞虽高表达肝细胞标志基因,而肝内其他细胞的标志基因则不表达或低表达。RT-PCR检测显示原代肝细胞可表达IL-10和IL10Rα。台盼兰细胞计数提示IL-10干预48h,I组平均细胞数仅为C组的71.96%(P<0.05);MTT检测亦显示IL-10干预24、48h,I组吸光度值分别为C组的88.41%与90.24%(P<0.05);流式细胞术检测结果表明IL-10干预24h,I组肝细胞峰DNA含量是C组的59.06%,I组较C组降低(P<0.01),甚至低于N组(P<0.01)。结论:分离的原代肝细胞纯度较高,大鼠原代肝细胞表达IL-10/IL10R mRNA,IL-10抑制大鼠原代肝细胞增殖。     

Immunoregulatory properties of IL-13 in patients with inflammatory bowel disease; comparison with IL-4 and IL-10

Activated monocytes with increased expression of proinflammatory cytokines play a major role in inflammatory bowel disease (IBD). Immunoregulatory cytokines such as IL-4 and IL-10 can effectively suppress the proinflammatory response of activated monocytes. IL-13 is a recently described antiinflammatory agent in vitro. The aim of our study was to determine the in vitro immunosuppressive capacity of IL-13, IL-4 and IL-10 in patients with IBD. Peripheral blood monocytes were isolated from 27 patients with ulcerative colitis (UC), 27 patients with Crohn's disease (CD) and 16 healthy controls. Cells were stimulated with pokeweed mitogen (PWM) after treatment with IL-13, IL-4 and IL-10, and secretion of IL-1β, tumour necrosis factor-alpha (TNF-α) and IL-6 was assessed using sandwich ELISA systems. Peripheral blood monocytes secreted significantly increased amounts of TNF-α and IL-6 under stimulation with PWM in patients with CD, while UC patients showed significantly elevated levels of IL-1β. The antiinflammatory cytokines IL-13, IL-4 and IL-10 were all capable of inhibiting monocyte secretion of IL-1β in a dose-dependent manner. With regard to IL-13 and IL-4, there was no significant suppression of TNF-α and IL-6 in patients with active IBD. By contrast, IL-10 was able to down-regulate all proinflammatory cytokines in active IBD as well as in controls. Proinflammatory cytokines from patients with inactive IBD could be significantly down-regulated by all three immunoregulatory cytokines. The inhibitory effect of IL-13 on TNF-α and IL-6 production in differentiated macrophages was diminished in IBD patients, as well as in controls. In disease controls we also observed a reduced inhibition of TNF-α and IL-6 after treatment with IL-13. In conclusion, the antiinflammatory activity of IL-13 is partially reduced in patients with active IBD. The hyporesponsiveness of activated and differentiated monocytes to IL-13 and IL-4 does not seem to be a disease-specific phenomenon.