Bcl-2基因多态性与系统性红斑狼疮相关性的研究

目的：明确中国人群中bcl-2基因多态性是否与系统性红斑狼疮（SLE）相关,检测Bcl-2与IL－10易感等位基因间是否存在协同作用。方法：通过荧光标记微卫星分型技术对232个SLE核心家系及106例正常对照进行Bcl-2微卫星的基因分型。结果：（1）两组对象Bcl-2等位基因和主要基因型分布频率差异有显著意义（P值分别为0．001和0．003）;（2）Bcl-2等基因存在传递不平衡,Bcl-2-195bp等位基因从父母优势传递给患病子代（传递：不传递＝122：82,P＝0．0051）;（3）同时携带Bcl-2-195bp和和IL－10G138bp易感等位基因的个体较单独携带Bcl-2-195bp ak IL-10G138bp的个体,患病的危险性增加（OR值分别为3．00,1．77和1．07）,结论：Bcl-2基因多态与SLE发病相关,其可能直接参与SLE发病或与附近某个易感位点存在连锁不平衡 。Bcl-2与IL－10易感等位基因在决定SLE易感中存在协同作用。     

染色体1q23.2区域存在与中国人群系统性红斑狼疮发病相关基因位点

目的：明确中国人群中Bcl-2基因多态是否与系统性红斑狼疮（SLE）相关,检测Bcl-2与IL－10易感等位基因是否存在协同作用。方法：通过荧光标记微卫星分型技术对232个SLE核心家系及106例正常对照进行Bcl-2微卫星的基因分型。结果：（1）两组对象Bcl-2等位基因和主要基因型分布频率差异有显著意义（P值分别为0．001和0．003）;（2）Bcl-2等位基因和主要基因型分布频率差异有显著意义（P值分别为0．001和0．003）;（2）Bcl-2等位基因存在传递不平衡,Bcl-2－195bp等位基因从父母优势传递给患病子代（传递：不传递＝122：82,P＝0．0051）;（3）同时携带Bcl-2－195bp和IL－10G138bp易感等位基因的个体较单独携带Bcl-2-195bp或IL－10G138bp的个体,患病的危险性增加（OR值分别为3．00,1．77和1．07。结论：Bcl-2基因多态与SLE发病相关,其可能直接参与SLE发病或附近某个易感位点存在连锁不平衡。Bcl-2与IL－10易感等位基因在决定SLE易感中存在协同作用。     

Preeclampsia: a multifactorial disease resulting from the interaction of the feto-maternal HLA genotype and HCMV infection

PROBLEM: To clarify the possible influence of human leukocyte antigen (HLA) mother-child genotypes and human cytomegalo virus (HCMV) presence on the development of preeclampsia. METHODS OF STUDY: One hundred and four DNA samples from mothers with preeclampsia, mothers with a normal history of pregnancies and their neonates were tested by polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) for HLA-A, -G, -DRB1, -DQA1, -DQB1 alleles. The HCMV sequences were analyzed using a PCR-SSOP method and the four primers described by Chou (Chou S: J Clin Microb 1992; 30:2307-2310). RESULTS: Compared with their respective controls, a significant increase of DRB1*07 among neonates (P(c) = 0.05) and of DRB1*07 and/or DRB1*06 among pre-eclamptic mothers (P(c) = 0.003, RR = 8,5) was found. When HCMV sequences were detected in pre-eclamptic mothers carrying those phenotypes the RR increased up to 40. Furthermore, the fetal inheritance of a maternal HLA-G*0104 increased the risk for the appearance of the disease (RR = 30; P = 0.025). CONCLUSION: The results suggest that the presence of alleles HLA-G*0104, DRB1*07/06, HCMV sequences and the fetal inheritance of maternal G*0104, should be considered as conditioning factors for the development of preeclampsia.     

肝脂酶基因启动子250G/A多态性与冠心病的关系

目的探讨本地区汉族人肝脂酶(HL)基因启动子250G/A多态性与冠心病的关系。方法采用聚合酶链反应限制性片段长度多态性(PCR-RELP)技术检测了103例冠心病患者和69名健康对照组汉族人HL启动子250G/A多态性基因型,探讨了其对血脂、载脂蛋白水平的影响。结果冠心病组的基因型和等位基因频率分布与正常老年组之间的差异无统计学意义;冠心病组的高密度脂蛋白胆固醇(HDL-C)载脂蛋白A1(apoA1)水平与正常老年组同基因型之间的差异具有统计学意义(P<0.05);冠心病组的apoA1水平(1.20±0.31)g/L明显低于正常老年组的同基因型(1.49±0.23)g/L;冠心病组的HDL-C水平(1.30±0.31)mmol/L明显高于同组的无突变型(1.16±0.32)mmol/L。经多元Logistic逐步回归分析的显示,TG是冠心病危险因子,apoA1是保护因子(P<0.05),但未见A等位基因是一个危险因子。结论在冠心病患者中,HL启动子250G/A基因多态性对血脂水平有一定影响。     

等位基因特异-荧光定量PCR检测胱硫醚-β-合成酶基因T833C/G919A点突变及其与糖尿病肾病的关联性初步观察

目的建立胱硫醚-β-合成酶（CBS）基因T833C、G919A点突变的等位基因特异-荧光定量PCR（TaqMan—ARMS）测定方法，探讨2型糖尿病肾病患者CBS基因T833C、Gg19A点突变率及与糖尿病肾病（DN）的相互关系。方法采用PCR时引物3’端错配扩增阻滞（ARMS）原理，结合荧光定量PCR技术（TaqMan探针），制备野生和突变质粒标准品，建立野生引物和突变引物2个反应体系，根据荧光定量PCR时野生引物循环阈值（Wct）与突变引物循环阈值（Mct）的比值△ct（△ct=Wct／Mct）及扩增有无指数增长期出现，建立点突变等位基因型的判定标准，并对94例DN患者（组1）和140例尿微量白蛋白正常的非糖尿病对照者（组2）的CBS基因T833C、Gg19A点突变进行检测。结果建立的TaqMan-ARMS方法检测T833C野生等位基因型的判定标准为Act〈0．72或Met〉40，杂合突变型为0．9〈Act〈1．10，纯合突变型为1．40〈Act或Wet〉40；G919A野生等位基因型判定标准为Act〈0．74或Mct〉40，杂合突变型为0．92〈Act〈1．03，纯合突变型为1．26〈Act或Wet〉40。T833C点突变TY、TC、CC3种基因型在DN组分布频率分别为98．94％、1．06％和0，组2中分别是99．29％、0．71％和0；两组人群833C等位基因频率分别为0．53％和0．36％，基因型和等位基因频率差异均无统计学意义。各组中未发现G919A等位基因杂合突变和纯合突变型。结论成功建立了测定CBS基因T833C、G919A点突变的TaqMan—ARMS方法，该方法准确、特异，适合高通量点突变的检测。本研究未观察到CBS基因T833C、G919A点突变为DN的遗传危险因素。     

北京地区CYP450药物代谢基因的等位基因分布调查

目的调查北京地区人口中的药物代谢酶系CYP450基因的等位基因分布情况,并推算CYP450基因多态性位点的等位基因丰度和近交系数。方法在北京地区抽样使用Taqman方法进行CYP450相关的基因型检测,估算出涉及北京地区人口中5个CYP基因中的6个SNP位点等位基因分布情况和近交系数。结果 CYP3A4表现出最大的等位基因丰度差别,CYP2D6表现出最小的等位基因丰度差别。结论 CYP2D6和CYP2C19两个基因的基因型在北京市人口中呈现较高的多态性分布,医师在使用涉及到这两个基因参与代谢的药物时,可以参考CYP450基因型检测结果。     

2+0 CYP21A2 deletion carrier — a limitation of the genetic testing and counseling: A case report

BACKGROUNDCYP21A2 gene mutations may all cause reduction or loss of 21-hydroxylase activity, leading to development of congenital adrenal hyperplasia (CAH) with different clinical phenotypes. For families with CAH children, genetic testing of the parents and genetic counseling are recommended to assess the risk of recurrence.CASE SUMMARYWe report a case of CAH with a high suspicion before delivery. The risk of the child suffering from CAH during the pregnancy had been underestimated due to the deviation of genetic counseling and genetic testing results. Our report confirmed a CYP21A2 homozygous deletion in this case, CYP21A2 heterozygous deletion in the mother, and a rare 2+0 CYP21A2 deletion in the father.CONCLUSIONIt is important to analyze the distribution of CYP21A2 gene in the two alleles of parents of children with CAH.     

重症肌无力患者肿瘤坏死因子等位基因α-308多态性分析

目的研究肿瘤坏死因子α(TNFα)等位基因α-308多态性与重症肌无力(MG)发病的关系。方法MG患者100例及健康对照100名,行聚合酶链反应(PCR)扩增全血基因组TNFα启动子-328～-98片段(210bp),NcoⅠ限制性内切酶酶切-308位点,检测等位基因频率。结果MG患者TNFα-308A等位基因频率(0.32)高于健康对照组(0.21,P<0.05)。在发病年龄≥40岁患者组,该基因频率(0.34)较此年龄健康对照组(0.10)高(P<0.05),但此等位基因与患者性别分布无关。在疾病的类型中,等位基因A与Osserman分型以及是否合并胸腺病变无关。结论MG的发病可能与此基因相关,尤其是发病年龄大的患者。     

急性缺血性卒中ApoEε4等位基因与血脂和预后相关性研究

目的探讨急性缺血性卒中患者载脂蛋白E(Apo E)ε4等位基因与血脂水平及预后的关系。方法据Apo E基因分型和美国国立卫生研究院卒中量表(NIHSS)评分,将786例急性缺血性卒中患者分为携带Apo Eε4等位基因组和不携带Apo Eε4等位基因组,以及预后良好组(NIHSS评分≤10分)和预后不良组(NIHSS评分10分),分别采用单因素和前进法多因素Logistic回归分析筛查影响携带Apo Eε4等位基因急性缺血性卒中患者预后的不良因素。结果携带Apo Eε4等位基因组患者血清低密度脂蛋白胆固醇和载脂蛋白B表达水平高于不携带Apo Eε4等位基因组[(3.25±0.85)mmol/L对(3.00±0.83)mmol/L,P=0.008;(1.20±0.30)mmol/L对(1.09±0.25)mmol/L,P=0.000]。前进法多因素Logistic回归分析仅入院时NIHSS评分和出院时改良Rankin量表评分是影响急性缺血性卒中患者预后的主要危险因素(均P=0.000),而Apo Eε4等位基因并非其影响因素(P=0.343)。结论携带Apo Eε4等位基因的急性缺血性卒中患者血清低密度脂蛋白胆固醇和载脂蛋白B表达水平升高,但Apo Eε4等位基因并非预后不良的预测指标。     

Prognostic significance of complement alleles Bf and C4 in early rheumatoid arthritis

Summary The prognostic significance of class III major histocompatibility complex complement components, factor B (Bf), C4A and C4B, were studied in a 3-year prospective study of 73 patients with early RA. Patients with C4B null allele had higher disease activity with more radiological progression than patients with C4A null allele or patients without null alleles. C4B null allele also associated with increased susceptibility to side effects from antirheumatic treatment. The Bf phenotypes did not associate with the severity of RA. C4B null allele may have prognostic significance in determining a special subgroup of RA patients with a more complicated course of the disease.