凝血酶活化纤维蛋白溶解抑制物基因编码区C1040T及G753A的多态性与脑梗死的相关性

目的探讨中国汉族脑梗死患者凝血酶活化纤维蛋白溶解抑制物(TAFI)基因编码区C1040T及G753A单核苷酸多态性与脑梗死的相关性。方法回顾性分析采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测130例脑梗死患者和118名同期行正常体检者(对照组)的TAFI基因编码区C1040T及G753A的多态性。结果脑梗死组TAFI基因G753A多态性的GG型频率41.5%(54例),A等位基因携带者频率58.5%(76例);而对照组分别为GG型频率44.9%(53例),A等位基因携带者频率55.1%(65例)。TAFI基因G753A多态性的GG型及A等位基因携带者两组频率差异无统计学意义(χ2=0.288,P=0.592)。在脑梗死组,C1040T多态性的CC型占50.0%(65例),T等位基因携带者占50.0%(65例);而对照组分别为CC型51.7%(61例),T等位基因携带者占48.3%(57例)。C1040T多态性的CC型及T等位基因携带者两组差异无统计学意义(χ2=0.071,P=0.790)。多因素Logistic回归分析显示,TAFI基因编码区G753A单核苷酸多态性(GA或AA基因型)及C1040T单核苷酸多态性(CT或TT基因型)不是脑梗死发病的独立危险因素。结论 TAFI基因编码区C1040T及G753A的多态性与脑梗死之间无显著相关性,不是脑梗死发病的独立危险因素。     

编码TAFI505A/G和1040C/T基因多态性与2型糖尿病关系的研究

目的：探讨凝血酶激活的纤溶抑制物（TAFI）编码区2个位点（505A/G,1040C/T）的单核苷酸多态性与2型糖尿病（T2DM）发病及病程进展的相关性。方法：应用聚合酶链反应-限制性内切酶片段长度多态性（PCR-RFLP）分析技术检测267例T2DM患者（单纯糖尿病110例,早期糖尿病肾病90例,临床糖尿病肾病67例）和140例正常对照者的TAFI505A/G、1040C/T2位点的多态性。结果：505A/G多态性位点病例组与对照组中各基因型的分布差异无统计学意义。在1040C/T位点,T2DM组T等位基因的频率与对照组相比明显下降（15.6%对25.7%,P〈0.05）,其T/T纯合子型比例亦显著下降（P〈0.05,95% OR 0.28,CI0.11～0.70）。但这种显著性差异只在早期糖尿病肾病患者中表现出来,随着病情的进展,这种差异在临床糖尿病肾病患者组与对照组间却表现不明显,差异无统计学意义（P〉0.05）。结论：1040C/T多态性位点T等位基因可能作为一种保护性基因在T2DM发病及早期病情进展中起到保护性作用,即TAFI1040C/T基因多态性可能与T2DM患病危险度存在关联。     

凝血酶活化纤维蛋白溶解抑制物基因编码区G505A单核苷酸多态性与脑梗死的关系

目的探讨中国汉族人群中凝血酶活化纤维蛋白溶解抑制物（TAFI）基因编码区G505A单核苷酸多态性与脑梗死的关系。方法采用聚合酶链反应一限制性片段长度多态性（PCR-RFLP）技术,检测130例脑梗死患者和118例同期体检者的TAFI基因编码区G505A的多态性。结果脑梗死组TAFI基因G505A的GG基因型占35．4％（46／130）,GA＋AA基因型占64．6％（84／130）;而对照组分别为49．2％（58／118）、50．8％（60／118）,差异有统计学意义（P=0．028）。脑梗死组G、A等位基因频率分别为60．4％（157／260）、39．6％（103／260）,对照组分别为69．9％（165／236）,30．1％（71／236）,差异有统计学意义（P=0．026）。多因素Logistic回归分析显示,TAFI基因编码区G505A单核苷酸多态性（GA或AA基因型）是脑梗死发病的独立危险因素（OR=2．660,95％CI：1．330-5．317,P=0．006）。结论TAFI基因G505A的多态性可能是脑梗死的危险因素之一。     

内皮型一氧化氮合酶基因G894T多态性与蒙古族原发性高血压合并卒中的关系

目的探讨内皮型一氧化氮合酶（eNOS）基因G894T多态性与蒙古族原发性高血压及原发性高血压合并卒中之间的关系。方法选择长期生活在内蒙古乌拉特后旗、三代血亲内无其他民族的蒙古族人群286例,其中原发性高血压合并卒中组70例,原发性高血压组104例,正常血压组112名。采用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）技术检测3组eNOS基因G894T多态性。结果原发性高血压合并卒中组eNOS基因G894T位点GG、GT＋TT基因型频率为75.7%、24.3%,G、T等位基因频率为86.4%、13.6%;原发性高血压基因型频率为81.7%、18.3%,等位基因频率为89.9%、10.1%;正常血压组基因型频率为93.8%、6.2%,等位基因频率为96.9%、3.1%。3组基因型频率及等位基因频率比较,差异均有统计学意义（χ2=12.240,OR=4.811,95%CI：1.879~12.318;χ2=14.175,OR=4.868,95%CI：1.990~11.909;χ2=7.358,OR=3.353,95%CI：1.346~8.351;χ2=8.647,OR=3.481,95%CI：1.448~8.372）,原发性高血压合并卒中组与原发性高血压组比较,差异均无统计学意义（χ2=0.601,OR=1.329,95%CI：0.646~2.734;χ2=0.993,OR=0.398,95%CI：0.720~2.709）。结论eNOS基因G894T多态性的T等位基因与蒙古族人群原发性高血压及原发性高血压合并卒中的发生可能相关。     

斑秃与CTLA-4基因外显子1 A/G49多态性研究

目的探讨细胞毒性T淋巴细胞相关抗原4（CTLA-4）基因外显子1第49位点A/G多态性是否与斑秃的遗传易感性有关。方法采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）对56例斑秃患者和124例正常对照者的CTLA-4基因外显子1的第49位点进行基因分型。结果斑秃患者CTLA-4基因第一外显子第49位点基因型频率与正常对照组比较差异无统计学意义（χ^2=1.768,P〉0.05）;斑秃患者CTLA-4基因第一外显子第49位点等位基因频率与正常对照组比较差异无统计学意义（χ^2=1.676,P〉0.05）。结论CTLA-4基因第一外显子第49位碱基A→G多态性与斑秃的发病可能无相关性。     

中高海拔地区2型糖尿病患者抵抗素基因多态性与代谢相关脂肪性肝病相关性的研究

目的 探讨中高海拔地区T2DM患者抵抗素（RETN）基因多态性与代谢相关脂肪性肝病（MAFLD）的相关性。方法 选取青海地区T2DM患者400例,根据肝脏超声检查分为单纯T2DM组（n=200）及T2DM合并MAFLD组（T2DM+MAFLD,n=200）,同期选取我院体检健康者180名为正常对照（NC）组。采用ELISA法检测受试者RETN,PCR测序法检测RETN基因-420C/G及+299G/A位点多态性。结果 T2DM+MAFLD组G/G基因型频率和G等位基因频率高于NC、T2DM组（P<0.05）,C/C基因型频率和C等位基因频率低于NC、T2DM组（P<0.05）,C/G、G/G基因型及G等位基因可增加T2DM合并发生MAFLD风险的1.571、2.126和1.537倍。Logistic回归分析显示,-420C/G位点G/G基因型是T2DM合并MAFLD的危险因素。T2DM+MAFLD组A等位基因频率高于NC、T2DM组（P<0.05）,G等位基因频率低于NC、T2DM组（P<0.05）,等位基因A较G增加T2DM合并MAFLD风险的1.432倍。结...     

血管紧张素转换酶基因I/D多态性及醛固酮合成酶基因T-344C多态性与蒙古族人群原发性高血压的相关性研究

目的研究血管紧张素转换酶（ACE）基因及醛固酮合成酶（CYP11B2）基因多态性与蒙古族原发性高血压（EH）的关系。方法应用PCR-RFLP技术检测98例EH患者与正常对照组108名健康受试者ACE基因第16内含子I/D多态性及CYP11B2基因T-344C多态性。结果①蒙古族人ACE基因I/D位点II、ID、DD基因型频率在EH组和正常对照组分别为0.44、0.38、0.18和0.42、0.32、0.26，差异无显著性（χ^2=1.693，P=0.192）；②I、D等位基因的频率分别为0.63、0.37和0.58、0.42，差异无显著性（χ^2=0.808，P=0.363）；③CYP11B2T-344C位点TT、TC、CC基因型的频率在EH组和正常对照组分别为0.46、0.44、0.09和0.37、0.54、0.09，两组之间差异无显著性（χ^2=0.005，P=0.945）。④T、C等位基因频率分别为0.69、0.31和0.64、0.36，差异无显著性（χ^2=0.928，P=0.335）；⑤同时分析CYP11B2基因T-344C基因型与ACE基因I/D基因型在蒙古族人群患EH方面无协同作用。结论ACE基因I/D位点及CYP11B2基因T-344C位点与蒙古族人群患EH无相关性。     

脂联素基因SNP-11377多态性与冠脉病变程度相关性研究

目的探讨在中国上海地区汉族人群中脂联素基因（APM1）启动子序列单核苷酸多态性（SNP）与冠脉病变程度的关系。方法采用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法，分析了325例冠脉造影结果和脂联素启动子序列单核苷酸多态性（-11377G／C）的关系．研究设立了冠心病组（CAD）和正常对照组，并根据冠脉造影结果按照不同病变支数及Gensini评分将分成不同病变组，分析-11377位点基因型及基因频率的差异性。结果（1）冠心病组脂联素基因-11377位点多态性GC、GG基因型频率与对照组比较，显著高于对照组，差异有极显著性（χ^2=12．619，P〈0．05）；（2）冠心病患者脂联素-11377位点G等位基因频率显著高于正常人（χ^2=11．291，P〈0．05）；（3）根据冠脉造影结果冠脉不同病变支数各组比较，脂联素-11377位点基因型差异无显著性（χ^2=11．575，P〉0．05），而等位基因频率具有显著差异性（χ^2=11．582，P〈0．05）；（4）按Genisini标准冠状动脉不同积分各组之间比较脂联素基因型间差异无显著性（χ^2=10．983，P〉0．05），但等位基因频率具有显著差异性（χ^2=8．978，P〈0．05）。结论脂联素SNP-11377G／C各种基因型与冠心病有关，与冠状动脉粥样硬化病变程度无关，而等位基因频率不但与冠心病显著相关，并且与冠状动脉病变程度有关。     

细胞毒T淋巴细胞相关抗原4基因多态性与溃疡性结肠炎

目的炎症性肠病的发病与T细胞过度活化有关,细胞毒T淋巴细胞相关抗原4（CTLA-4）是重要的T细胞活化负性调节因子.本课题研究CTLA-4基因启动子区-1722位点（T/C）及-1661位点（A/G）多态性与中国汉族人群中溃疡性结肠炎（UC）的相关性.方法采用PCR-限制性片段长度多态性方法,对87例中国汉族UC患者和116例正常对照者进行CTLA-4基因-1722位点和-1661位点多态性检测.结果UC患者CTLA-4基因-1661位点A/G＋G/G基因型频率,-1661位点G等位基因频率显著高于正常对照组（34.5%比15.5%,P=0.002,OR=2.865,95%CI=1.467～5.596;19.0%比8.2%,P=0.002,OR=2.624,95%CI=1.435～4.796）;而在-1722位点的基因型频率、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CTLA-4基因启动子区-1661位点G等位基因与中国汉族UC存在显著相关性.     

MTHFR基因多态性与肺血栓栓塞症的关系

目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性与肺栓塞的关系。方法选取肺栓塞患者102例及同期住院或门诊患者及健康体检者120例,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法进行检测两组MTHFR基因C677T、A1298C位点的多态性,比较两组基因型和等位基因分布频率。结果 1在肺栓塞组中,MTHFR C677T位点CC、C/T、TT基因型频率分别为20.6%、31.4%、48%,在对照组中分别为29.2%、39.1%、31.7%,在两组中TT基因型频率差异有统计学意义(P=0.013)。在两组间,T等位基因分布频率差异有统计学意义(P=0.008)。2在肺栓塞组中,MTHFR A1298C位点AA、A/C、CC基因型频率分别为23.5%、31.4%、45.1%,在对照组中分别为31.7%、37.5%、30.8%,在两组中CC基因型频率差异有统计学意义(P=0.029),等位基因C分布频率两组间差异有统计学意义(P=0.018)。结论MTHFR基因C677T位点的TT基因型及A1298C位点的CC基因型多态性可能为肺血栓栓塞症的高危因素。     

Plasma thrombin-activatable fibrinolysis inhibitor levels and Thr325Ile polymorphism as a risk marker of myocardial infarction in Egyptian patients

OBJECTIVE: The objective of this study was to investigate whether thrombin activatable fibrinolytic inhibitor (TAFI) Thr325Ile polymorphism and TAFI antigen (Ag) levels could constitute a risk marker of myocardial infarction (MI) in Egyptian patients. STUDY POPULATION AND RESULTS: The study included forty-six patients with acute MI (mean age 55.7 +/- 8.1 years, 33 men, 13 women) compared with age and sex-matched healthy volunteers (n = 54) as a control group. Clinical examination, laboratory investigations, electrocardiography (ECG) and/or echocardiography were done. TAFI Thr325Ile (reference sequence: rs1926447) polymorphism was genotyped in both studied groups using TaqMan SNP (single nucleotide polymorphism) genotyping assay. The genotypes of the high-risk allele [Thr/Ile (CT) and Ile/Ile (TT)] were significantly more frequent in patients compared with the control group (54.4% and 32.6% vs. 51.8% and 5.6%, respectively) and were also associated with an increased risk of MI [OR = 4.95, (95% CI: 1.80 - 13.63); P = 0.0001]. Ile325 allele carriers were more frequent in cases than in control subjects (60.0% vs. 31.5%) [OR = 3.26, (95% CI = 1.82 - 5.83), P = 0.001]. The Thr325Ile SNP significantly correlated with TAFI antigen levels with the C/C genotype corresponding with the highest and the T/T genotype with the lowest TAFI antigen levels (P < 0.001). No statistically significant relation was found between TAFI Thr325Ile polymorphism and either the type or the site of MI. CONCLUSIONS: TAFI Thr325Ile and its respective plasma protein level could have a contribution to MI risk in the Egyptian population.This could be helpful in refining a risk profile for coronary heart disease (CHD) patients.     

Thrombin-activatable fibrinolysis inhibitor in young patients with myocardial infarction and its relationship with the fibrinolytic function and the protein C system

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a fibrinolytic inhibitor. Studies in coronary artery disease have reported increased TAFI activity (TAFI Act) and low TAFI antigen (TAFI Ag) levels. This controversy might be explained by the polymorphisms of its gene. Only the Thr325Ile polymorphism modulates both TAFI Ag and Act levels in vitro. This study assessed TAFI Ag and Act levels, TAFI Thr325Ile polymorphism, the fibrinolytic and protein C systems and some prothrombotic mutations in a young patient group (n = 127, aged < 51 years, with myocardial infarction) and a control group (n = 99) with similar characteristics. Patients exhibited hypofibrinolysis and higher plasminogen activator inhibitor-1 (PAI-1) levels. Although TAFI Ag was lower, TAFI Act level was significantly higher in patients and positively correlated with PAI-1, protein C inhibitor and the euglobulin lysis time. No differences between groups were found according to the Thr325Ile polymorphism. Irrespective of the genotype, patients had higher TAFI Act levels. The Ile-325 variant exhibited lower TAFI Ag levels. We suggest that the hypofibrinolysis observed in these patients results from an increase in both PAI-1 and TAFI Act, which is not related to the Thr325Ile polymorphism. Patients have high TAFI Act with low TAFI Ag levels, probably because of an increased stability of TAFI related to a fibrinolytic hypofunction.     

Association between thrombin activatable fibrinolysis inhibitor genotype and levels in plasma: comparison of different assays

Thrombin activatable fibrinolysis inhibitor (TAFI) antigen levels exhibit a large interindividual variability in which genetic control seems to play a major role. However, recent reports have questioned the association between TAFI concentration and genotype, suggesting that variable antibody reactivity towards TAFI isoforms, particularly the Thr325Ile polymorphism (1040C/T), may lead to artefacts in TAFI antigen levels. In order to compare assay outcome we determined plasma TAFI levels in 92 healthy individuals, using an enzyme-linked immunosorbent assay (ELISA) (commercial antibodies), an electroimmunoassay (in-house antibodies) and a commercial chromogenic assay (Actichrome TAFI). Each individual was genotyped for the -438A/G and 1040C/T polymorphisms in the TAFI gene. TAFI levels were significantly associated with genotype in both antigen and chromogenic assays. All assays displayed significant correlations with each other. Linear regression and Bland-Altman agreement analysis in the genotype subgroups showed that neither the genotype nor the concentration affected the relationship between the Actichrome TAFI and the electroimmunoassay. In contrast, the ELISA/Actichrome TAFI and the ELISA/electroimmunoassay relationships were concentration- and genotype-dependent. Our results demonstrate that artefacts may arise when measuring TAFI antigen levels by ELISA. Nevertheless, the electroimmunoassay and the Actichrome TAFI assay support a genotype-related variation of TAFI concentration.     

TCF7L2基因单核苷酸多态性与汉族2型糖尿病遗传易感性关系的研究

目的探讨TCF7L2基因单核苷酸多态性与汉族人2型糖尿病遗传易感性的关系。方法无血缘关系江苏地区汉族人1535例,分为2型糖尿病组（T2DM）、糖耐量减低组（IGT）和正常糖耐量组（NGT）,LDR法检测TCF7L2基因rs7903146（C／T）及rs12255372（G／T）单核苷酸多态性。结果（1）T2DM、IGT组rs7903146位点T等位基因频率均高于NGT组,但差异无统计学意义;（2）糖代谢异常组rs7903146位点CT基因型频率及T等位基因频率则显著高于NGT组（P均〈0．05）,T等位基因参与糖代谢异常发生的相对风险为1．589,人群归因危险度为2．1％。结论TCF7L2基因单核苷酸多态分布存在明显的种族异质性,rs7903146位点T突变可能是中国汉族人群糖代谢异常发生的遗传因素之一。     

转化生长因子-β1基因多态性与 HBV 感染风险的相关性研究

目的：探讨转化生长因子-β1（ TGF-β1）基因多态性与中国人群HBV感染敏感性的关系。方法：本研究为以中国人群为研究对象的病例-对照研究,随机纳入50例HBV感染者（观察组）和50例与病例组性别、年龄相匹配的健康者（对照组）。采用聚合酶链反应-限制性片段长度多态性分析法检测TGF-β1基因T29 C多态性。结果：病例组和对照组基因型和等位基因分布均有明显差异（χ2＝12.795, df＝2, P＝0.002;χ2＝10.895, df ＝1, P＝0.002）。携带基因型TC和CC感染HBV的风险显著升高（ OR＝4.227,95％CI：1.604～11.139, P＝0.004; OR＝8.250,95％CI：2.042～33.334, P＝0.003）。携带等位基因C较等位基因T感染HBV的风险显著升高（ OR＝2.631,95％CI：1.472～4.702, P＝0.001）。结论： TGF-β1基因T29C多态性可能与HBV感染风险有关。     

干扰素诱导抗病毒蛋白基因多态性与慢性丙型肝炎疗效相关性研究

目的探讨α-干扰素（IFN-α）诱导的黏病毒抵抗蛋白（MxA）和真核细胞起始因子调节区2（eIF-20α-reg2）基因的单核苷酸多态性（SNP）与慢性丙型肝炎（CHC）患者对IFN-α治疗应答的关系。方法前瞻性研究216例CHC患者，在接受IFN-α联合利巴韦林治疗48周，随访至停药后24周时，评价疗效[分为持续性应答（SVR）和非持续性应答（NSVR）]。应用多聚酶链反应（PCR）及限制性片段长度多态性（RFLP）法检测患者MxA启动子-88（G／T）、-123（C／A）及eIF-20α-reg2（MG）位点的SNP，并比较SNP与IFN疗效的关系。结果MxA 88位点：GT与GG型患者SVR（57．43％对34．21％）比较，差异有统计学意义（χ^2=9．37，P〈0．01）；TT与GG型患者SVR（66．67％对34．21％）比较，差异有统计学意义（χ^2=9．37，P〈0．01）。而GT与TT型患者SVR比较（57．43％对66．67％），差异无统计学意义（χ^2=1．00，P〉0．05）；MxA-123位点、eIF-20α-reg2位点基因型与IFN疗效比较：差异均无统计学意义（χ^2=4．87，P〉0．05；χ^2=1．66，P〉0．05）。多因素Logist回归分析结果显示：病毒载量（OR=3．178，95％CI：1．463～6．904，P=0．003）、干扰素种类（OR=3．117，95％CI：1．484～6．544，P=0．003）对SVR的独立影响具有统计学意义。MxA-88基因型（OR=1．470，95％CI：0．646～3．345，P=0．358）对SVR的独立影响无统计学意义。结论CHC患者MxA-88为TT或GT型者比GG型者对IFN-α应答好，但不是影响SVR的独立因素。