细胞间黏附分子1基因K469E多态性与冠状动脉粥样硬化性心脏病的关联研究

目的研究中国汉族人群中细胞间黏附分子1（intercellular adhesion moleculel，ICAM1）基因K469E多态性与冠状动脉粥样硬化性心脏病（简称冠心病）的关联。方法采用聚合酶链反应．限制性片段长度多态性方法检测了173例冠心病患者和141名对照的ICAM1基因K469E基因型和等位基因的分布。结果基因型频率符合Hardy-Weinberg平衡。冠心病组的KK基因型的频率显著高于对照组（64．2％比48．9％，P〈0．01），同样，冠心病组K等位基因的频率显著高于对照组（79．2％比69．9％，P〈0．01）。经Logistic回归分析排除年龄，性别，和冠心病其它危险因素的影响后，KK纯合子患冠心病的危险性是KE和EE基因型的2．35倍（95％CI：1．03-5．36，P〈0．05）。结论ICAM1基因K469E多态性与中国汉族人冠心病的危险性相关，其中K等位基因可能是冠心病的遗传危险因素。     

血浆活化凝血因子Ⅶ及其基因多态性与老年人冠状动脉粥样硬化性心脏病的相关分析

目的探讨血浆活化因子Ⅶ(activated coagubtionfactorⅦ,F7a)水平及其基因的MspⅠ多态性与老年人冠状动脉粥样硬化性心脏病的关系。方法采用候选基因及病例-对照的方法,以聚合酶链反应及限制性片段长度多态性分析技术,对108例老年冠状动脉粥样硬化性心脏病患者(冠状动脉粥样硬化性心脏病组)及120名年龄、性别匹配的健康人(正常对照组)行F7基因的MspⅠ多态性分析并确定基因型,同时采用重组可溶性组织因子法(rSTF2-219)测定血浆F7a水平。结果(1)老年冠状动脉粥样硬化性心脏病组血浆F7a水平显著高于正常对照组(2.88±0.62vs2.58±0.60μg/L,P<0.05),Logistic回归分析显示,血浆F7a水平与老年人冠状动脉粥样硬化性心脏病的危险性独立相关(OR1.21,P<0.05)。(2)F7基因型频率分布符合Hardy-Weinberg平衡,基因型及等位基因频率分布在两组间差异无统计学意义(P>0.05)。(3)两组血浆F7a水平均与F7基因多态性显著相关,RR基因型血浆F7a水平显著高于Q等位基因携带者(P<0.05)。结论血浆F7a水平增高是老年人冠状动脉粥样硬化性心脏病发病的独立危险因素,F7a水平受其基因的MspI多态性影响。     

PAI-1基因多态性与冠状动脉粥样硬化性心脏病患者预后的相关性研究

目的 研究汉族人群纤溶酶原激活物抑制物-1(plasminogen activator inhibitor-1,PAI-1)基因4G/5G多态性与冠心病(coronary artery disease,CAD)患者主要不良心脏事件(major adverse cardiovascular event,MACE)及冠脉病变严重程度的关联.方法 应用聚合酶链反应-限制性片段长度多态性分析155例冠心病患者及190名正常人PAI-l基因的4G/5G多态性,随访患者是否发生MACE,并分析PAI-1基因4G/5G多态性与冠脉病变的关联.结果 (1)冠心病组4G/4G型频率(58/155,37.42%)明显高于对照组(52/190,27.37%),差异有统计学意义(P＜0.01).(2)PAI-1基因4G/4G型频率在MACE组(40/81,49.38%)均明显高于无MACE组(18/74,23.42%),差异有统计学意义(P＜0.01);(3)冠心病患者中PAI-1基因4G/4G型频率在多支病变组(30/47,44.77%)明显高于单支病变组(9/37,24.32%),差异有统计学意义(P＜0.05).结论 携带PAI-l基因4G/4G基因型易患冠心病,易侵犯多支冠状动脉.     

冠状动脉粥样硬化性心脏病细胞问黏附分子1基因K469E多态性的研究

OBJECTIVE: To study the linkage between K469E polymorphism of intercellular adhesion molecule 1(ICAM1) gene with ICAM1 plasma level and coronary heart disease (CHD) in Han population of China. METHODS: One hundred and sixty-four controls without CHD and 160 patients with CHD were enrolled in our study. By nested PCR with allele-specific oligonucleotide primers, all patients and controls were genotyped for the ICAM1 polymorphism. And the ICAM1 plasma level was measured by ELISA. RESULTS: In the patients with CHD, both K allele frequency and the plasma level of ICAM1 were higher than those in control (P<0.05). The individual with K allele had higher plasma level of ICAM1 than that without K allele (344.34+/-128.59 microg/L vs 303.54+/-108.74 microg/L, P=0.008). K allele enhanced the risk of CHD (P<0.01, OR=2.158, 95%CI: 1.250-3.727). There was the K allele cooperation with smoking in influencing the risk of CHD. CONCLUSION: There is the polymorphism of ICAM1 K469E gene in Han population of China, and the K allele may be a genetic factor influencing the risk of CHD.     

纤维蛋白原Bβ链基因-1420G/A、-993C/T和-854G/A多态性与冠状动脉粥样硬化性心脏病的关联研究

目的调查健康人和冠状动脉粥样硬化性心脏病(简称冠心病)患者的纤维蛋白原B(fibrino-genB,FGB)β基因-1420G/A、-993C/T和-854G/A的基因多态性频率分布,以及与血浆Fg水平的关系。方法应用等位基因特异性PCR扩增技术和限制性片段长度多态性技术对186例冠心病患者和149名健康对照者进行分析。比浊法测定血浆Fg浓度。结果等位基因频率-1420A在冠心病组为0.33,在对照组为0.26,冠心病组明显比对照组升高,两者比较差异有统计学意义(P<0.05)。等位基因频率-993T和-854A在两组之间无差别。Logistic回归分析显示β-1420G/A与冠心病相关(OR=1.922,P=0.003)。冠心病组血浆Fg水平(3.87±1.75)g/L较健康人组(3.10±0.77)g/L明显升高,且差异有统计学意义(P<0·05)。结论纤维蛋白原Bβ-1420G/A可能与冠心病发病相关联。     

囊泡相关膜蛋白8基因多态性与冠状动脉粥样硬化性心脏病的相关性研究

目的 研究囊泡相关膜蛋白8(synaptobrevins/vesicle-associated membrane proteins 8,VAMP8)基因rs1010多态性在中国汉族人群中的分布及与冠状动脉粥样硬化性心脏病(简称冠心病)的相关性.方法 采用聚合酶链反应-限制性片段长度多态性技术,对汉族185例冠心病患者及149名正常人VAMP8 rs1010基因多态性,基因型及等位基因频率分布进行研究.结果 研究人群中存在VAMP8 rs1010基因多态性,基因型符合Hardy-Weinberg平衡,冠心病患者A等位基因频率显著高于对照组(67.3%VS 53.0%,P<0.05).Logistic回归分析得出:VAMP8基因(AA+AG)基因型是冠心病的独立危险因素,(AA+AG)基因型比GG基因型的比数比为1.969,95%可信区间为1.032～3.755.结论 VAMP8 rs1010基因多态性与冠心病有关,A等位基因可能是汉族人群冠心病的遗传危险因素.     

冠状动脉粥样硬化性心脏病细胞间黏附分子1基因 K469E多态性的研究

目的探讨细胞间黏附分子1(intercellularadhesionmolecule1,ICAM1)基因K469E多态性及其血浆水平与中国汉族冠状动脉粥样硬化性心脏病(简称冠心病)之间的关系。方法利用巢式PCR和免疫酶联吸附测定技术对160例冠心病患者和164名非冠心病对照进行ICAM1基因K469E多态性及其血浆水平的检测和对比分析。结果冠心病组K等位基因频率、ICAM1血浆水平均高于非冠心病对照组(P<0·05);含K等位基因的个体ICAM1血浆水平(344.34±128.59μg/L)高于不含K等位基因的个体(303·54±108·74μg/L),差异有统计学意义(P=0.008);且其患冠心病(心肌梗塞)的危险性升高(P=0.006,OR=2·158,95%CI:1.250~3.727);K等位基因与吸烟在影响冠心病发生危险性方面有协同作用。结论在中国汉族人群中存在ICAM1基因K469E多态性,其中K等位基因有可能是冠心病的遗传危险因素。     

白细胞介素10基因-627位点多态性与早发冠状动脉粥样硬化性心脏病的关系

目的探讨白细胞介素10（interleukin 10，IL10）基因-627位点多态性与早发性冠状动脉粥样硬化性心脏病（coronary heart disease，CHD）和血清IL10水平的关系。方法应用聚合酶链反应-限制性片段长度多态性办法，检测CHD患者163例和正常对照者112名IL10基因-627位点多态性，采用ELISA法检测血清IL10。结果IL10基因-627位点基因型和等位基因频率在CHD组和对照组之间差异无统计学意义，X^2值分别为1．9324，1．5703，P〉0．05。按性别分层分析，男性组X^2值分别为1．2708，0．8595，P〉0．05；女。女性组X^2值分别为0．8254，0．7127，P〉0．05。血清IL10在AA型、AC型和CC型之间差异有统计学意义，P〈0．05，但在CHD组和对照组之间差异无统计学意义，P〉0．05。结论IL10基因-627位点多态性与中国人汉族人冠病的易感性无显著关联，但可能影响IL10基因的转录活性。     

L-选择素基因多态性与冠状动脉粥样硬化性心脏病易感性的相关性研究

目的探讨L-选择素基因P213S多态性是否与冠状动脉粥样硬化性心脏病有关联。方法采用病例-对照研究，对212例经冠状动脉造影确诊的冠心病患者和230名正常对照者进行研究。应用聚合酶链反应限制性片段长度多态性（polymemse chain reaction-restriction fragment length polymorphism，PCRRFLP）技术测定L-选择素基因多态性。结果冠心病组213P等位基因频率明显高于对照组（77．59％vs69．35％，P=0．006）。PP纯合子患冠心病的风险是SS纯合子的2．70倍（95％CI：1．07～6．81），且经Logistic回归分析校正性别、年龄、体重指数、血清总胆固醇、甘油三酯、高密度脂蛋白-胆固醇和低密度脂蛋白-胆固醇等相关因素之后，差异仍具有统计学意义。根据冠状动脉造影结果进一步对冠心病患者进行分组后分析，发现L-广选择素基因P213S多态性与病变血管支数及疾病程度无相关性。结论L-广选择素213P等位基因可能与我国汉族人冠心病的易感性相关联。     

冠状动脉粥样硬化性心脏病患者载脂蛋白(a)五核苷酸重复序列基因多态性的初步研究

目的　探讨载脂蛋白 (a) [apolipoprotein(a) ,apo(a) ]五核苷酸重复序列 (pentanucleotiderepeats,PNR)基因多态性与中国汉族人冠状动脉粥样硬化性心脏病 (简称冠心病 )发病的关系。方法　应用聚合酶链反应结合聚丙烯酰胺凝胶电泳和硝酸银染色 ,对 15 3名中国汉族正常人和 16 5例冠心病患者apo(a) PNR基因多态性进行了分析。结果　冠心病组 apo(a) PNR(TTTTA) 5/8基因型频率 (0 .188)和(TTTTA) 5等位基因频率 (0 .115 )显著高于正常对照组 (0 .0 39,0 .0 2 6 ) ,差异有显著性 (P <0 .0 1,P<0 .0 5 )。结论　apo(a) PNR基因多态性与人群易患冠心病有关 ,可能在一定程度上参与了冠心病的发生和发展过程。     

Association between interleukin-17 gene polymorphisms and risk of coronary artery disease

We conducted a case-control study to estimate the association between IL-17A rs2275913, rs3819025 and rs3748067 polymorphisms and development of coronary artery disease. A total of 415 patients with coronary artery disease and 448 health controls were recruited during the period of March 2013 and October 2014. Genotyping of IL-17A rs2275913, rs3819025 and rs3748067 were analyzed by polymerase chain reaction coupled with restriction fragment length polymorphism. By logistic regression analysis, we found that individuals with the AA genotype (OR, 2.18; 95% CI, 1.35-3.56) and the GA+AA genotype (OR, 1.39, 95% CI, 1.06-1.84) of rs2275913 were associated with an increased risk of coronary artery disease when compared with the GG genotype. Individuals carrying the GA+AA genotype of rs2275913 were more likely to have a higher risk of coronary artery disease in those with hypertension and smoking habit, and the adjusted ORs (95% CI) were 3.92 (2.13-6.82) and 2.74 (1.71-4.40). In conclusion, we suggest that individuals with the AA genotype and the GA+AA genotype of rs2275913 are associated with an increased risk of coronary artery disease, especially in those with hypertension and smoking habit.     

载脂蛋白E-CI-CII基因多态性与冠状动脉粥样硬化性心脏病易感性的关系

目的　探讨载脂蛋白E- CI- CII基因簇多态性与冠状动脉粥样硬化性心脏病(冠心病)的关系。方法　采用多重扩增突变系统(multiplex amplification refractory mutation system ,multi- ARMS)和聚合酶链反应-限制性片段长度多态性法检测了2 0 3例患者和36 5名对照的apo E、CI、CII基因多态性;L INKAGE程序计算连锁不平衡系数D和D′。结果　病例组apo E基因E3/4基因型频率为0 .2 5 9、ε4等位基因型频率为0 .139,均高于对照组,差异有统计学意义(P<0 .0 5 ) ;apo C 基因H2等位基因型频率在病例组为0 .2 0 5 ,高于对照组的0 .113,差异有统计学意义(P<0 .0 5 ) ;apo CII基因多态性分布在两组间差异无统计学意义(P>0 .0 5 ) ;apo E、CI基因存在显著的连锁不平衡(D′=0 .6 72 ,P<0 .0 1) ,病例组ε4 - H2 - T1单倍型频率为5 .4 %高于对照组的0 .5 % ,差异有统计学意义(P<0 .0 5 )。调整混杂因素后,ε4、H2等位基因同时携带者吸烟呈显著的相乘交互作用,危险度(odds ratio,OR)及其95 %可信限(95 % confidenceinterval,95 % CI)为18. 3(2 .35～15 0 .81,P<0 .0 5 ) ,交互作用归因比(attributable proportions ofinteraction,API)为5 7.3% ;ε4、H2和多量饮酒三者间呈超相加作用,OR(95 % CI)为12 .7(2 .75 7～5 8.5 5     

SUMO4基因多态性与冠心病及2型糖尿病合并冠心病的关系

目的 探讨北京地区汉族人群小泛素样修饰蛋白4 (small ubiquitin-like modifier 4,SUMO4)基因多态性与冠状动脉粥样硬化性心脏病(coronary artery disease,CAD)及2型糖尿病(type 2 diabetes mellitus,T2DM)合并CAD的关系.方法 采用病例对照设计,入选369例单纯CAD患者(CAD组)、189例2型糖尿病合并CAD患者(T2DM+ CAD组)及500名健康个体(对照组).应用聚合酶链反应-高分辨熔解曲线技术结合测序验证法,检测SUMO4基因rs237025、rs237024及rs600739 3个单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点的基因型与等位基因在3组间的分布,并通过分层分析比较SNPs不同基因型携带者的临床相关危险因素的差异.结果 3个SNPs的等位基因和基因型在3组间的分布差异无统计学意义(P＞0.05);通过分层分析,在T2DM+CAD组发现rs237025各基因型携带者的甘油三酯水平、rs600739各基因型携带者的体重指数水平的差异有统计学意义(P值分别为0.020和0.049),但组间多重比较仅发现rs237025的GG基因型携带者较GA及AA基因型携带者具有更高的甘油三酯水平(P＜0.01).结论 SUMO4基因多态性可能与北京地区汉族人群伴或不伴T2DM的CAD易感性无关.     

Interaction between metabolic syndrome and PON1 polymorphisms as a determinant of the risk of coronary artery disease

Abstract The enzyme serum paraoxonase plays an important role in antioxidant defences and prevention of atherosclerosis. Metabolic syndrome (MS) is a clinical condition associated with increased oxidant stress and cardiovascular mortality. Two common polymorphisms of serum paraoxonase, PON1 Leu₅₅Met and Gln₁₉₂Arg, have been postulated to modulate the cardiovascular risk. We studied 915 subjects with angiographic documentation: 642 subjects with coronary atherosclerosis and 273 with normal coronary arteries. Two hundred and twenty-four subjects met the diagnostic criteria of MS. We found a significant interaction between MS and both the PON1 polymorphisms in determining the risk of coronary artery disease (P<0.05 by likelihood-ratio test). The 55Leu and the 192Arg alleles, associated with reduced protection against lipid peroxidation, were associated with coronary artery disease only in the MS subgroup. Subjects with MS and both 55Leu and 192Arg alleles had significantly increased risk (OR=9.38 with 95% CI=3.02–29.13 after adjustment by multiple logistic regression) as compared to subjects without MS and with 55Met/Met-192Gln/Gln genotype. No increased risk was found for subjects with MS and the 55Met/Met-192Gln/Gln genotype. This study highlights a potential example of genetic (paraoxonase polymorphisms)-clinical (MS) interaction influencing cardiovascular risk.     

Association of two polymorphisms in the FADS1/FADS2 gene cluster and the risk of coronary artery disease and ischemic stroke

Little is known about the association of the FADS1/FADS2 SNPs and serum lipid levels and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese southern population. The present study aimed to determine such association in the Chinese southern population. A total of 1,669 unrelated subjects (CAD, 534; IS, 553; and healthy controls, 582) were recruited in the study. Genotypes of the FADS1 rs174546 SNP and the FADS2 rs174601 SNP were determined by the SNaPshot Multiplex Kit. The T allele and TT genotype frequencies of the two SNPs were predominant in our study population. The T alleles were associated with increased risk of CAD and IS. Correspondingly, the C alleles were associated with reduced risk of CAD and IS. Haplotype analyses showed that the haplotype of T-T (rs174546-rs174601) was associated with an increased risk for IS, and the haplotype of C-C (rs174546-rs174601) was associated with a reduced risk for CAD and IS. The two SNPs were likely to influence serum lipid levels. The T allele carriers of the two SNPs and rs174601 TT genotype were associated with decreased serum HDL-C and ApoAI levels in the patient groups and with an increased risk of CAD and IS. The present study suggests that the FADS1 rs174546 SNP and the FADS2 rs174601 SNP are associated with the risk of CAD and IS, and are likely to influence serum lipid levels. However, further functional studies are needed to clarify how the two SNPs actually affect serum lipid levels and the risk of CAD and IS.     

An HphI polymorphism in the E-selectin gene is associated with premature coronary artery disease

An increased expression of E-selectin has been observed in the arterial endothelium interacting with lymphocytes and macrophages in human atherosclerotic lesions. We examined whether a polymorphism in the E-selectin gene, due to a G to T mutation (G98T) in the untranslated region of exon 2, was associated with premature coronary artery disease (CAD). Other lipid and nonlipid risk factors including a Ser to Arg (S128R) substitution in the E-selectin gene were also assessed. In patients with premature CAD (men < or = 45 years old and women < or =55 years old, N = 51) who underwent an elective diagnostic coronary arteriography, the frequency of the mutation was significantly higher than in controls (N = 50, 0.22 vs. 0.10, p = 0.024). After controlling for other CAD risk factors (plasma total cholesterol, triglyceride, LDL-apolipoprotein B. cigarette smoking and the S128R mutation) by multiple logistic analysis, the G98T mutation in the E-selectin gene was still a significant predictor of premature CAD [p = 0.022, odds ratio (95%, CI)= 3.58 (1.20-10.67)].     

PON2基因C311S、G148A多态性与脑卒中关系的研究

目的探讨对氧磷酶2（paraoxonase2,PON2）基因多态性与脑卒中的关系。方法用聚合酶链反应-限制性片段长度多态性分析法分别检测PON2基因C311S、G148A多态性在脑出血组（150例）、脑梗死组（180例）和正常对照组（120名）的基因频率。结果发现中国湖南地区人群存在PON2基因C311S、G148A多态性,在正常对照组中等位基因频率分别是S/C0.77/0.23,A/G0.43/0.57。脑出血组、脑梗死组患者PON2基因的等位基因频率与正常对照组相比差异无统计学意义（P〉0.05）。结论PON2基因多态性可能与中国湖南汉族人群脑卒中发病无关,C/S、G/A等位基因可能不是中国湖南地区汉族人群脑卒中发病的独立危险因素。     

结合珠蛋白基因1/2多态性与中国人冠心病易感性的关联研究

目的 通过分析冠心病患者及冠脉正常组中结合珠蛋白(haptoglobin,HP)基因1/2多态性分布,初步探讨HP基因1/2多态性与冠心病易感性的关系.方法 经冠脉造影确诊冠心病组189例,冠脉正常对照组242名;采用聚合酶链反应-限制性片段长度多态性技术检测所有受试者HP基因型.结果 冠心病组HP基因型分布与对照组相比差异有统计学意义(P=0.002),表现为HP2-2基因型在冠心病组的频率明显高于对照组(0.54vs.0.35,P=0.000),单因素分析显著增加冠心病的风险(OR=2.166,95%CI:1.467～3.196),HP2等位基因的频率也明显高于对照组(0.74 vs.0.61).同时,多因素Logistic回归分析表明HP2-2基因型是冠心病的独立危险因素(P=0.002;OR=2.101,95%CI:1.311～3.367).结论 HP2-2基因型与冠心病的发生相关,可能是冠心病发病的独立危险因子;HP2等位基因可能是中国人冠心病的易感基因.

Abstract：

Objective To assess the association of haptoglobin (HP)1/2 polymorphism with coronary heart disease (CHD) in Chinese Hans. Methods One hundred and eighty-nine CHD patients and 242 healthy controls confirmed with angiography were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was utilized to genotype the HP1 and HP2 alleles and genotype frequencies in cases and controls were compared. Results The frequency of HP2-2 genotype was significantly higher in CHDs than in controls (0. 54 vs. 0.35, P=0.000). The HP2-2 genotype significantly increased the risk for CHD in univariable analysis (OR= 2. 165, 95% CI: 1. 467-3. 196). Multifactor Logistic regression analysis indicated that HP2-2 genotype is an independent risk factor to CHD (P=0.002;OR=2. 101, 95% CI: 1. 311-3. 367). Similarly, the HP2 allele frequency in the CHD group was significantly higher than that in the control subjects (0.74 vs. 0. 61, P= 0. 000). Conclusion The HP2-2genotype is associated with CHD in Chinese. HP2-2 genotype may be an independent risk factor to CHD,and HP2 allele may be a genetic susceptibility factor to CHD in Chinese.     

Lipoprotein lipase gene PvuII polymorphism serum lipids and risk for coronary artery disease: meta-analysis

Our aim was to determine whether lipoprotein lipase gene PvuII polymorphism can be considered as an independent risk factor for coronary artery disease (CAD) by conducting a meta-analysis of all available published trials, including our own study. In 7 seperate studies, 3289 subjects were screened for this substitution; meta-analysis included only some of these individuals. Among the 7 studies, 6 were performed on white subjects, whereas 1 was on patients with Saudi Arabic descent.Subgroup analysis indicated that individuals with PvuII substitution does not have an increased risk for CAD. The LPL-PvuII genotype and allele frequency distributions did not differ significantly between CAD patients and healthy controls. There was no difference in the distribution of LPL-PvuII genotypes between the healthy subjects and the patients with CAD. However, no significant differences in lipid variables (triglyceride and HDL-cholesterol) were determined for the PvuII polymorphisms in the patients with CAD. No significant differences were found in serum triglyceride and HDL-cholesterol levels for LPL-PvuII genotypes when the control and CAD groups were pooled. In conclusion, LPL-Pvu II polymorphism cannot be used as independent genetic risk factor for CAD.