慢性乙型肝炎患者E-选择素A561C基因多态性的研究

目的研究中国河北地区汉族人群E-选择素(E-selectin)A561C基因多态性与慢性乙型肝炎的相关性.方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测91例慢性乙型肝炎患者和85名健康对照组的E-selectin基因多态性.结果中国河北地区汉族人群中E-selectin A561C存在AA、AC和CC三种基因型,E-selectin A561C多态性在慢性乙型肝炎组和对照组间的分布差异显著(χ2=5.96,P＜0.05).AC CC基因型患慢性乙型肝炎的风险是AA基因型的2.89倍(OR=2.89,95% CI:1.20～6.94).等位基因频率在两组间差异也有显著性(χ2=6.14,P＜0.05,OR=2.23,95% CI:1.02～4.85).结论中国河北地区汉族人群中存在E-selectin A561C位点单核苷酸多态性,其基因多态性与慢性乙型肝炎的感染具有相关性,C等位基因可能是中国河北地区慢性乙型肝炎发病的易感因素之一.     

蛋白激酶Cξ亚型基因多态性与2型糖尿病的相关性

目的 研究中国东南方汉族人群2型糖尿病家系的蛋白激酶Cξ亚型基因多态性,探讨其与2型糖尿病(T2DM)易感性的关系.方法 应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法,对来自T2DM家系成员、无家族史的T2DM患者及正常对照的该基因rs381664位点进行基因分型.结果 rs381664位点基因型、等位基因频率在各组人群中分布差异无统计学意义.按年龄分层显示在家系大于50岁人群组中,突变型CC/CT型为保护性因素[OR 95% CI＝0.541 (0.323～0.905)].按BMI分层分析糖尿病相关生物学指标显示,在家系内对照组超重者和病例组肥胖者中,均发现携带TT基因型个体的胰岛素抵抗指数显著高于携带CC/CT型个体(P＜0.05).结论 蛋白激酶Cξ亚型基因rs381664位点多态性与胰岛素抵抗存在相关性,在50岁以上人群的T2DM发生中可能起到一定作用.     

载脂蛋白M基因多态性与冠心病的相关性

目的 检测载脂蛋白M(ApoM)基因rs805264位点、rs707922位点和rs707921位点的多态性在贵州省汉族人群的分布,探讨其多态性与冠心病(CHD)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)方法检测220例CHD患者和195例对照组的基因型,以酶法测定血脂水平.结果 ApoM基因rs805264位点、rs707922位点及rs707921位点等位基因G-G-C、A-T-A紧密连锁,CHD组A-T-A单体型显著高于对照组.CHD组及对照组A-T-A单体型血清总胆固醇水平显著高于G-G-C单体型组,高密度脂蛋白胆固醇低于G-G-C单体型组.结论 贵州汉族人群ApoM基因rs805264、rs707922和rs707921位点A-T-A单体型可能是CHD的潜在遗传致病危险因子.     

白介素-13基因多态性与哮喘的相关性研究

目的探讨白介素-13(IL-13)基因多态性与哮喘的相关性。方法用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)方法检测96例汉族哮喘儿童及96名汉族健康儿童IL-13基因内含子区+1923位点的基因型和等位基因频率,分析此位点单核苷酸多态性与哮喘的易感性、血浆总IgE(TIgE)、IL-13水平的相关性。结果+1923位点等位基因C、T频率在两组间分布具有显著性差异(P<0.01),等位基因T与哮喘关联,OR(T/C)=1.87,95%CI=1.25～2.80,P<0.01。两组基因型(TT、CT、CC)频率的分布亦有显著性差异(P<0.01),哮喘组中TT、CT基因型人群外周血IL-13及TIgE水平与同组及对照组CC基因组比较有显著性差异(P<0.01)。结论 IL-13基因+1923位点多态性是影响哮喘的重要候选基因,T等位基因与哮喘关联,并可能通过增强IL-13基因的表达影响血浆总IgE水平。     

纤维蛋白原Bβ链基因启动区2个多态位点与冠心病的相关性

目的 研究纤维蛋白原(Fg)Bβ链基因启动区上游-148C/T及-455G/A多态性位点与冠心病(CAD)及血浆Fg水平的相关性.方法 90例CAD患者及年龄、性别相匹配的115例正常对照者,聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测FgBβ-148C/T及-455G/A基因型,比较两组基因型及等位基因频率分布及不同基因型间血浆Fg水平.结果 CAD组-148CC基因型频率较对照组减少;而CT及TT基因型较对照组增加;CAD组C等位基因频率为70.56%,对照组为86.09%(P＜0.01).而-455G/A多态位点频率在两组间无显著差异.-148C/T及-455G/A多态性位点均影响CAD组及对照组血浆Fg水平,但对冠脉受累支数无影响.结论 FgBβ-148C/T多态性与中国人群CAD及血浆Fg水平相关,T等位基因可能是中国人群CAD的遗传易患因子.     

IL-10 基因多态性及血清水平与颅内动脉瘤发病的关系

目的 分析白细胞介素（IL）-10 基因启动子区－ 1082G/A、－ 819C/T 单核苷酸多态性（SNP）及血清 IL-10 水平与颅内动脉瘤（IAs）发病的关系。 方法 运用 PCR 及 DNA 直接测序的方法, 检测 206 例 IAs 患者（IAs 组）和 187 例非 IAs 患者（对照组）的 IL-10 基因启动子区 SNP 位点, － 1082G/A、－ 819C/T 的基因型频率和等位基因频率, χ2检验分析 IAs 组和对照组之间的差异; 采用 ELISA 法检测血清中 IL-10 水平, t 检验分析 2 组之间的差异。 结果 IL-10 基因启动子区－ 1082G/A 位点的 GG 基因型和 GA＋ AA 基因型, 以及 G 等位基因和 A 等位基因频率比较, IAs 组较对照组 GA＋ AA 基因型以及 A 等位基因频率更高, 差异均有统计学意义（P < 0.01）, GA＋ AA 基因型（OR 值为 4.137, 95%CI 2.476~6.914）和 A 等位基因（OR 值为 3.368, 95%CI 2.476~4.583）携带者有更高的 IAs 发病风险; IL-10 基因启动子区－ 819C/T 位点的 CC 基因型和 CT＋ TT 基因型以及 C 等位基因和 T 等位基因频率比较, IAs 组较对照组 CT＋ TT 基因型以及 T 等位基因频率更高, 差异均有统计学意义（P < 0.01）, CT＋ TT 基因型（OR 值为 3.393, 95% CI 1.952~5.900）和 T 等位基因（OR 值为 3.764, 95%CI 2.730~5.192）携带者有更高的 IAs 发病风险。 IAs 组血清 IL- 10 水平低于对照组（P < 0.01）。 结论 IL-10 基因启动子区 SNP 影响 IL-10 表达,IL-10 基因启动子区－ 1082G/A、－ 819C/T 多态性与 IAs 的发病有关。     

ABCA1启动子区基因多态性与血脂水平及冠心病的关系

目的：检测三磷酸腺苷结合盒转运子A1(ATP binding cassette transporter 1,ABCA1)基因启动子-14bp单核酸多态性(single nucleotide polymorphism,SNP) 位点与天津市汉族人群冠心病发生(coronary heart disease,CHD)及血脂水平的关系。方法：采用病例对照研究,聚合酶链反应-限制性片段长度多态性(Polymerase Chain Reaction-Restriction Fragment Length Polymorphism)方法,对228例经冠状动脉造影确诊的冠心病患者和同一地区造影排除冠心病正常对照200例,进行ABCA1基因-14bp位点SNP分析检测,比较不同基因型与血脂水平和冠心病的关系。结果：ABCA1基因-14bp位点多态性有三种：CC、CT和TT型。全部检测人群中CC型占42.99%,CT型占51.64%,TT型占5.31%。冠心病组与对照组中CC、CT、TT三种基因型频率差异无统计学意义（p＞0.05）;冠心病患者与正常人等位基因频率差异无显著性（p＞0.05）;T等位基因携带者HDL-C水平低于非携带者（p＜0.05）。结论：ABCA1基因-14bp位点多态性与冠心病发生无相关性;T等位基因携带者血浆HDL-C水平低下。     

血管紧张素Ⅱ受体基因多态性与醛固酮腺瘤发病风险的相关性

目的 探讨血管紧张素Ⅱ 1型受体及2型受体基因(AT1R、AT2R)多态性与中国汉族人群肾上腺醛固酮腺瘤(APA)发病风险的相关性.方法 提取148例APA组织DNA及192例正常人群外周血DNA;采用MGB-Taqman探针法对AT1R基因(rs5182、rs5186)和AT2R基因(rs5194、rs1403543) 4个SNP位点进行基因型检测.SNPassoc 1.5-3软件分析Hardy-Weinberg平衡以及AT1R、AT2R基因多态性与APA发病危险的关联性.结果 4个位点基因型分布均符合Hardy-Weinberg平衡(P均＞0.05).APA组AT2R基因rs5194位点A等位基因频率(0.49)要高于正常人群组(0.35)(x2=12.08,P==0.001).以rs5194纯合子基因型GG为参照,纯合子基因型AA和杂合子基因型GA的APA发病风险均增高(OR=2.66,95％ CI=1.45-4.87和OR=1.67,95％ CI=1.02-2.74).rs5194位点多态性在显性模型、隐性模型以及加性模型中均与APA发病相关联(OR=1.94,95％CI=1.23-3.06,P=0.003; OR=2.01,95％ CI=1.17-3.45,P=0.01; OR=1.64,95％CI=1.21-2.20,P=0.001).结论 AT2R基因rs5194位点多态性和APA发病相关联,对该SNP位点的检测可能可以对预测APA的发病危险提供有用的遗传信息.     

慢性乙型和丙型肝炎病毒感染与白细胞介素-4-589基因多态性的关系

目的 研究慢性乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)感染与白细胞介素(IL)-4-589基因多态性(SNP)的关系,探讨其免疫遗传机制.方法 对438名研究对象检测HBV、HCV感染标志物,筛选出健康对照者74例和感染者203例,其中HBV合并HCV感染组79例,单纯HBV感染组69例,HCV感染组55例.用Beckman LX-20全自动生化仪检测丙氨酸氨基转移酶(ALT),逆转录套式聚合酶链技术(RT-n-PCR)检测HCV-RNA表达,并分析IL-4-589 SNP,观察SNP与慢性HBV或HCV感染、HCV病毒复制和ALT的关系.结果 IL-4-589位点基因型和等位基因频率与感染类型和HCV-RNA复制均无关系(P＞0.05);IL-4-589位点基因型和等位基因频率ALT≥80 U/L组与＜80 U/L组比较差异有统计学意义(P＜0.01);携带CT和CC基因型肝脏损伤的OR值是TT基因型的3.43和8.25倍;携带C等位基因的肝脏损伤的风险是T等位基因的2.31倍.结论 IL-4-589位点CT、CC基因型和C等位基因能增加HBV和(或)HCV感染者的肝脏炎性损伤.     

天津地区人群中LOX-1基因3'-UTR多态性与冠心病的关系

目的:研究天津地区人群中凝集素样氧化低密度脂蛋白受体-1(LOX-1)3′-非编码区(3′-UTR)188位点基因多态性情况,探讨LOX-1基因多态性与冠心病(CAD)及血脂水平的关系。方法:冠心病组170例,均经冠脉造影(CAG)确诊;对照组140例,均经CAG排查。应用聚合酶链反应-限制片段长度多态性(PCR-RFLP)法对研究对象的LOX-1基因3′-UTR188位点多态性进行分析,并用自动生化分析仪检测血浆血脂水平。结果:冠心病组和对照组比较,LOX-1基因3′-UTR 188位点基因型频率和等位基因频率差异均无统计学意义(均P>0.05);在总研究对象中T等位基因携带者(CT+TT)与CC基因型者血三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、脂蛋白(a)[Lp(a)]水平差异均无统计学意义(均P>0.05),冠心病组与对照组中的CT+TT基因型者以上血脂水平差异亦无统计学意义(P>0.05)。结论:天津地区人群中LOX-1基因3′-UTR188位点多态性与冠心病的发病及血脂水平均无明显关系,其不能作为冠心病的预测因素。     

三磷酸腺苷结合盒转运子A1启动子区及7外显子基因突变与合并糖尿病的冠心病关联研究

目的首次研究汉族人群冠心病合并糖尿病与三磷酸腺苷结合盒转运子A1（ABCA1）基因启动子区-565C／T及7外显子R219K基因多态性关联分析。方法应用连接酶检测反应法对172例合并糖尿病冠心病患者及393例对照组测试-565C／T及R219K基因型。结果合并糖尿病冠心病患者-565C／T位点CC、CT及TT基因型频率分别为0．360（n=63）,0．482（n=83）,0．157（n=27）,与对照相比,TT基因型及T等位基因频率分别为0．157vs0．163,0．398vs0．409（均P〉0．05）。R219K位点AA＋AG基因型合并糖尿病的冠心病组与对照组分别为0．65vs0．73,P=0．079。关联分析显示,AA基因型系冠心病保护性因素,[OR=0．428（95％C10．227—0．603）,P=0．009]。结论ABCA1基因-565C／T位点T等位基因与合并糖尿病的冠心病无关联,R219K的A等位基因在合并糖尿病的冠心病组频率较低,提示A等位基因系冠心病保护性因子。     

Inflammation and atherosclerosis: the role of TNF and TNF receptors polymorphisms in coronary artery disease

Inflammation plays an important role in the pathogenesis of atherosclerosis and coronary syndromes; moreover, various lines of evidence suggest that genetic factors contribute significantly to the risk of coronary artery disease (CAD). Through its effects on endothelial function, coagulation, insulin resistance and lipid metabolism, the proinflammatory cytokine TNF could be involved in cardiovascular pathophysiology. The aim of our study is to analyze whether TNF gene promoter (-308 G/A; -857 G/A) and TNF receptor polymorphisms (TNFR1 MspA1 I exon 1 and TNFR2 Nla III exon 6) show involvement in CAD predisposition in a group of Italian patients compared with healthy controls. Genotyping was performed by PCR-RFLP. Consecutive Italian patients with angiographically proven CAD (n= 248) were compared with controls (n=241), matched for age, sex and geographical origins. CAD patients showed a higher frequency of the TNF -308 A allele than healthy controls (p=0.046). After stratification according to risk factors for CAD, our analysis revealed that CAD patients with diabetes (p=0.042) and CAD patients without hypertension (p= 0.0495) displayed a higher frequency of the TNF -308 AA genotype compared with healthy controls. Our data stress the inflammatory nature of CAD and show a possible involvement of TNF -308G/A promoter polymorphisms in the predisposition to the development of this disease. The less frequent A allele seems to be a predisposing factor for development of CAD in particular pathological settings associated with the disease itself, such as diabetes.     

A common variant of the angiotensinogen gene and the risk of coronary artery disease in a German population

The thymidine to cytosine transition at position 704 in exon 2 of the angiotensinogen gene leads to the amino acid substitution of threonine for methionine (T235 variant) and is responsible for elevated plasma levels of angiotensinogen. To examine the influence of T235 on the risk of coronary artery disease (CAD) we genotyped 184 CAD patients, 77 controls in whom CAD was excluded angiographically, and 155 healthy controls without signs of CAD by polymerase chain amplification and restriction enzyme digestion. Allele frequencies for A (wildtype) and a (mutant allele) in the total study population were 0.538 and 0.462, 0.536 and 0.464 in the healthy controls, and 0.481 and 0.519 in patients with excluded CAD, respectively. The allele frequencies and the genotype distribution in these groups did not show a significant difference. In conclusion, we did not observe an association between the T235 variant of the angiotensinogen gene and the risk of CAD.     

A genetic variant of apolipoprotein M increases susceptibility to coronary artery disease in a Chinese population

1. High-density lipoprotein (HDL) is widely accepted as a lipoprotein that protects against coronary artery and other atherosclerotic diseases. Recently, a new apolipoprotein encoded by the APOM gene, which plays an important role in affecting the intrinsic properties of HDL, has been reported. Genetic variations exist in the APOM gene, but their significance is presently unclear. The aim of the present study was to elucidate whether the APOM T-855C mutant allele is implicated in coronary artery disease (CAD). 2. In the present study, 418 patients with CAD and 372 controls were studied, all of whom were Han Chinese from Jiangsu Province, China. Plasma levels of triglycerides (TG), total cholesterol (TC), HDL-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) were evaluated. Genomic DNA from the whole blood from these subjects was subjected to polymerase chain reaction amplification and restriction enzyme digestion to determine genotype with respect to the APOM T-855C polymorphism. 3. The allelic frequencies were in Hardy-Weinberg equilibrium. Plasma HDL levels were significantly lower in subjects with CAD than in control subjects (1.08 +/- 0.31 vs 1.25 +/- 0.32, respectively; P < 0.001) and the distribution of genotypes and allelic frequencies was significantly different in the two groups (P = 0.013 and 0.005, respectively). Multiple logistic regression analysis after adjustment for age, gender, smoking, body mass index, hypertension and serum glucose showed that, compared with the wild-type TT genotype, carriers of the C allele had an increased risk of CAD (odds ratio = 1.819, 95% confidence interval 1.142-2.898; P = 0.012). 4. In conclusion, the results of the present study suggest that the APOM T-855C polymorphism carries an increased risk for CAD in this Chinese population.     

血清尿酸水平与高血压及冠心病发病关系的探讨

目的 探讨血清尿酸水平与高血压及冠心病发病之间的关系。方法 临床诊断为原发性高血压患者100例,其中高血压合并冠心病30例,冠心病60例,健康体检者100例,测定以上人员血尿酸水平,并对比分析。结果高血压并冠心病组及冠心病组血清尿酸水平明显升高,与高血压组比较有显著性差异(P<0.05),高血压组、冠心病组血尿酸水平与健康组比较有显著性差异(P<0.01)。结论 尿酸水平与高血压及冠心病的发生密切相关,高尿酸血症可能是致高血压、冠心病的独立危险因素。     

Biochemical investigation of rs1801282 variations in PPAR-γ gene and its correlation with risk factors of diabetes mellitus in coronary artery disease

We aimed to investigate the association of single nucleotide polymorphism of Pro/Ala (rs1801282) in peroxisome proliferator-activated receptor-gamma (PPAR-γ) gene with risk factors of diabetes mellitus (DM) in cardiovascular disease (CVD) patients. We recruited 244 participants from Faisalabad Institute of Cardiology and Department of Cardiology, Sargodha District Head Quarter Teaching Hospital, Pakistan. Out of 244 participants, 144 cases were CVD patients and 100 were healthy controls. CVD patients were further divided into 111 coronary artery disease (CAD) and 33 cardiomyopathy (CMP) patients. Assessment of variant specific polymorphism/mutation of Pro/Pro and Pro/Ala genotypes was done through amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Further, serum biomarkers were measured to investigate the association among risk factors of DM and Pro/Ala polymorphism in PPAR-γ gene. About 31.5% Pro/Ala genotype was found in CVD patients out of which 22.5% were CAD patients and 9% were CMP patients. As a result, obesity, hypertension and smoking (35%, 23%, 21%, respectively) were observed to be the most critical risk factors accompanying Pro/Ala mutation in PPAR-γ particularly in CAD patients as compared to that in CMP patients. A similar pattern of association was observed among the elevated levels of glucose, cholesterol, triglyceride and ALT with Pro/Ala mutation in CAD patients. Further, CAD patients using ACE inhibitors (18%) and β-blockers (13%) were found to be the carriers of Pro/Ala genotype and also showed significant increase in glucose level. This study suggests that hyperglycaemia in CAD patients particularly obese, smokers and hypertensives having Pro/Ala polymorphism in PPAR-γ gene are at high risk of developing DM as clearly observed by hyperglycaemia in CAD patients.     

Association between plasma homocysteine levels and coronary artery disease: a population-based study in northern Greece

OBJECTIVE: Elevated plasma total homocysteine (tHcy) levels constitute a risk factor for coronary artery disease (CAD). We prospectively examined the association of fasting tHcy levels in patients in Northern Greece who had established CAD. PATIENTS AND METHODS: Plasma fasting tHcy levels were measured in 42 patients with angiographically documented CAD and compared to 42 age-, sex-, BMI- and smoking habit-matched control subjects. We also determined the plasma vitamin B(12), folic acid and lipoprotein levels in all patients and controls. Conventional risk factors for CAD were also estimated. RESULTS: In a univariate analysis, tHcy (micromol/l) levels were higher in patients compared to controls almost reaching statistical significance (13 (7-41) vs 11.3 (4-39); p= 0.07). Multivariate analysis of conventional risk factors showed that tHcy levels were not an independent risk factor for CAD. However, tHcy levels were significantly higher in patients with a previous history of myocardial infarction compared to patients without such a history and to controls (15 (8.8-29) vs 11.7 (7-41); p = 0.007 and 15 (8.8-29) vs 11.3 (4-39); p = 0.002, respectively). Hyperhomocysteinaemia (> 15 micromol/l) was detected in 35.7% of patients and 11.9% of controls (p < 0.05). CONCLUSIONS: In Northern Greece, plasma tHcy levels may not be an independent risk factor for CAD in patients with angiographically documented CAD. However, patients with CAD have a trend towards higher tHcy levels. Additionally, plasma tHcy levels may be associated with the development of myocardial infarction.     

PCSK9基因单核苷酸多态性与冠心病的关联研究

目的:研究前蛋白转化酶枯草杆菌蛋白酶/西布曲明9a型(proprotein convertase subtilisin/kexin 9,PCSK9)基因多态性与冠状动脉粥样硬化性心脏病(coronary artery disease,CAD)的发病关系及对血脂水平、CAD病变严重程度和预后的影响.方法:对184例正常人和212例CAD患者采用聚合酶链反应-限制性片段长度多态性方法检测PCSK9基因多态性,检测CAD患者的病变支数及随防出院后心血管事件.结果:CAD组中G等位基因频率高于对照组(P=0.001),CAD组中GG基因型的总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白-胆同醇(low density lipoprotein-cholesterol,LDL-C)含量比AA基因型增高(P值分别为0.023、0.000、0.036),在CAD组中G等位基因携带者与AA基因型患者相比,出院后2年心血管事件增加(P=0.004,OR=2.013,95％CI∶1.225～3.018).结论:中国汉族人群基因多态性PCSK9基因E670G多态性可能与CAD发病相关;E670G基因多态性可能与CAD预后相关;PCSK9基因E670G多态性与冠脉狭窄程度无关.     

Association between plasma homocysteine levels and coronary artery disease: a population-based study in northern Greece

SUMMARY

Objective: Elevated plasma total homocysteine (tHcy) levels constitute a risk factor for coronary artery disease (CAD). We prospectively examined the association of fasting tHcy levels in patients in Northern Greece who had established CAD.

Patients and methods: Plasma fasting tHcy levels were measured in 42 patients with angiographically documented CAD and compared to 42 age-, sex-, BMI- and smoking habit-matched control subjects. We also determined the plasma vitamin B12, folic acid and lipoprotein levels in all patients and controls. Conventional risk factors for CAD were also estimated.

Results: In a univariate analysis, tHcy (jumol/l) levels were higher in patients compared to controls almost reaching statistical significance (13 (7–41) vs 11.3 (4–39); p?=?0.07). Multivariate analysis of conventional risk factors showed that tHcy levels were not an independent risk factor for CAD. However, tHcy levels were significantly higher in patients with a previous history of myocardial infarction compared to patients without such a history and to controls (15 (8.8-29) vs 11.7 (7-41); p?=?0.007 and 15 (8.8-29) vs 11.3 (4-39); p?=?0.002, respectively). Hyperhomocysteinaemia (> 15|imol/l) was detected in 35.7% of patients and 11.9% of controls (p?<?0.05).

Conclusions: In Northern Greece, plasma tHcy levels may not be an independent risk factor for CAD in patients with angiographically documented CAD. However, patients with CAD have a trend towards higher tHcy levels. Additionally, plasma tHcy levels may be associated with the development of myocardial infarction.