早发冠心病心肌梗死型与非心肌梗死型危险因素差异分析

目的探讨早发冠心病中心肌梗死型与非心肌梗死型的危险因素差异。方法回顾性分析2004年1月至2009年12月在沈阳医学院附属奉天医院心血管内科住院并确诊的45岁及以下冠心病患者165例,分为急性心肌梗死(AMI)组和非AMI组。对两组患者的相关临床资料及危险因素进行统计分析。结果 AMI组吸烟史比例、男性比率、血浆纤维蛋白原及D-二聚体均高于非AMI组,差异有统计学意义(P<0.05),两组的血脂异常率、血小板计数(PLT)、血小板压积、凝血酶原时间(PT)、国际标准化比值(INR)和活化部分凝血活酶时间(APTT)的差异无统计学意义。结论吸烟、男性性别、血脂水平异常是早发冠心病重要危险因素;血浆纤维蛋白原水平增高对于预测早发冠心病心肌梗死可能具有一定的临床意义。     

Lack of association between common polymorphisms in genes of the renin-angiotensin system and mortality after myocardial infarction

The insertion/deletion (I/D) polymorphism in the ACE gene and the A1166C polymorphism in the AT1R gene have been associated with left ventricular remodelling and prognosis after acute myocardial infarction (AMI). We investigated whether these genetic variants associate with impaired left ventricular ejection fraction (LVEF) and increased risk for in-hospital mortality after AMI. Consecutive AMI patients were recruited on admission and were genotyped for the above-mentioned polymorphisms. The frequency of the studied genotypes did not differ significantly between deceased patients and those who survived. The LVEF did not differ among patients with or without the DD genotype (45 +/- 10 vs. 45 +/- 10%, p = 0.892) or the CC genotype (45 +/- 10 vs. 46 +/- 10%, p = 0.859). These data question the role of the studied genotypes in the pathogenesis of AMI and do not support the previously supported hypothesis that these genotypes influence prognosis after AMI.     

The paradoxical association of common polymorphisms of the renin-angiotensin system genes with risk of myocardial infarction.

BACKGROUND: The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) and the A1166C polymorphism of the angiotensin-II AT1 receptor (AT1R) have been extensively investigated as possible risk factors for myocardial infarction (MI). DESIGN AND METHODS: Genetic association, case-control study, specifically designed to investigate the association of the above-mentioned polymorphisms with risk of MI in a homogeneous, low coronary risk, Caucasian population. The study population consisted of 1603 consecutive patients with acute MI who were recruited from nine clinics, located in three cities, and 699 unrelated adults who were randomly selected from the city catalogues. RESULTS: In univariate analysis, the DD genotype was found to be more prevalent among controls (40.8 vs. 35.2%, P=0.011). In multivariate analysis adjusted for age, gender, smoking status, diabetes mellitus, hypercholesterolaemia, hypertension and family history of coronary artery disease, the presence of the DD genotype was independently and negatively associated with risk of AMI (RR=0.743, 95% CI=0.595-0.927, P=0.008). The CC genotype was not found to be significantly associated with risk of MI, either in univariate (6.2 vs. 6.4%, P=0.856), or in multivariate analysis adjusted for the same confounders (RR=0.743, 95% CI=0.473-1.167, P=0.197). CONCLUSIONS: Contrary to previous reports, in this study the DD genotype of the ACE gene, but not the CC genotype of the AT1R gene, was associated with a lower risk of MI. Our results emphasize the complexity of genotype-phenotype interactions in the pathogenesis of ischaemic heart disease and question the previously hypothesized role of the DD genotype on risk of acute myocardial infarction.     

Methylenetetrahydrofolate reductase gene polymorphism and risk of premature myocardial infarction

BACKGROUND: Elevated plasma homocysteine level is an independent risk factor for cardiovascular disease. A common mutation (nucleotid 677C-T) in the gene coding for methylenetetrahydrofolate reductase (MTHFR) has been reported to reduce the enzymatic activity of MTHFR and is associated with elevated plasma levels of homocysteine, especially in subjects with low folate intake. HYPOTHESIS: Methylenetetrahydrofolate reductase T/T genotype may be a risk factor for premature MI in Turkish population who are known to have low folate levels. METHODS: The study group was comprised of 96 men (aged <45 years) with premature myocardial infarction (MI) and 100 age- and gender-matched controls who had no history or clinical evidence of coronary artery disease (CAD) and/or MI. DNA was extracted from peripheral blood and genotypes were determined by polymerase chain reaction, restriction mapping with HinfI, and gel electrophoresis. Conventional risk factors for CAD were prospectively documented. RESULTS: Allele and genotype frequencies among cases and control subjects were compatible with Hardy-Weinberg equilibrium. The frequencies of T/T, C/T, and C/C genotypes among patients with MI and control subjects were 15.6, 40.6, and 43.8%, and 5, 35, and 60%, respectively. Multivariate analyses identified smoking, MTHFR C/T polymorphism, diabetes mellitus, family history of CAD, and hypertension as the independent predictors of premature MI. Defining patients with non-T/T genotype (C/C and C/T combined) as reference, the relative risk of MI for subjects with T/T genotype was 5.94 (95% confidence interval: 1.96-18.02, p = 0.0016). CONCLUSIONS: Our findings suggest that C677T transition in the MTHFR gene may be a risk factor for premature MI in Turkish men.     

Tryptophanyl-tRNA synthetase gene polymorphisms and risk of incident myocardial infarction

Tryptophanyl-tRNA synthetase (WARS) gene polymorphisms have been associated with the patho-physiology of vascular angiogenesis and homeostasis. Data from a recent genome-wide linkage analysis suggested a potential role of WARS in the risk of myocardial infarction. However, no genetic-epidemiological data are available. From a prospective cohort of 14,916 initially healthy American men, we evaluated five common polymorphisms within or close to the WARS locus, all with a minor allele frequency >0.10, amongst 386 individuals who subsequently developed myocardial infarction and 386 matched individuals who remained free of reported cardiovascular events during follow-up. The polymorphisms were: a G > C substitution in the 5'-flanking region (dbSNP rs2273804), an A > G substitution in intron 1 (dbSNP rs941931), a 335T > C substitution in exon 10 (dbSNP rs9453), a C > T substitution in intron 10 (dbSNP rs1570305), and a C > T substitution in the C14orf68 region (dbSNP rs3736951). The observed genotypes were in Hardy-Weinberg equilibrium in the control group. Genotype- and haplotype-frequency distributions were similar between cases and controls. Further investigation using a haplotype-based matched logistic regression analysis, adjusting for age, smoking, randomized treatment-assignment (likelihood ratio test: chi(3)(2) = 3.20, p = 0.36) or with additional adjustment for BMI, hypertension, and diabetes (likelihood ratio test: chi(3)(2) = 2.38, p = 0.50) yielded similar null findings. An alternative haplotype analysis based on evolutionary arguments again yielded null results. In conclusion, we found no evidence for an association between the common polymorphisms or haplotypes of the tryptophanyl-tRNA synthetase gene tested and risk of myocardial infarction.     

Cardiovascular risk factors and lifestyle associated with premature myocardial infarction diagnosis

Young and old patients with acute myocardial infarction have different risk factor profiles, clinical presentation, angiographic findings and prognosis. In the present study we investigated the clinical profile of patients aged <46 years with acute myocardial infarction.Full English text available from: www.revespcardiol.org     

Genotypic interactions of renin-angiotensin system genes in myocardial infarction

BACKGROUND: Three-gene interactions among the genetic polymorphisms of the renin-angiotensin system (RAS) associated with acute myocardial infarction (AMI) have not been examined in a single population. We hypothesized that all types of gene-to-gene associations may occur in AMI, but that some will have a higher risk, depending on the gene frequencies. METHODS: Polymorphisms of the AGT (M235T), ACE (I/D) and AGTR1 (A1166C) genes in AMI patients and controls were analyzed using the polymerase chain reaction. Classic coronary risk factors were analyzed in all individuals. RESULTS: Logistic regression analysis of these factors and the genetic polymorphisms demonstrated that smoking, family history of CAD, arterial hypertension and total cholesterol were the most significant contributors to AMI. The genotypic frequencies for all three genes alone were similar between the infarction and control groups, with no increased risk of developing AMI. Double homozygous combinations for normal alleles (MM of AGT, II of ACE and AA of AGTR1) had a lower risk of AMI (odds ratio<0.38), indicating a protective effect in these individuals. In genotypic combinations that included at least one unfavorable allele, the risk (odds ratio) of developing AMI was 2.92, 2.63 and 2.68 for AGT vs. ACE, AGT vs. ATR1 and ACE vs. AGTR1, respectively. The positive interaction among the three genes and the risk of AMI had an odds ratio of 3.78 with a 95% CI of 0.88-12.85. CONCLUSIONS: The risk of developing AMI is higher whenever there are unfavorable alleles in gene-to-gene associations in the RAS.     

Five prothrombotic polymorphisms and the prevalence of premature myocardial infarction

We studied 5 functional hemostatic polymorphisms in 281 patients with premature myocardial infarction and in 530 control subjects. The role of these polymorphisms when analyzed independently is small, if any. However, the simultaneous combination of factor XIII and prothrombin polymorphisms exacerbated the risk. (OR=12.12; p=0.028). Moreover, combinations of factor V Leiden with prothrombin, and factor XII with prothrombin polymorphisms were only identified in patients. Our results support the relevance of gene-gene interactions in myocardial infarction.     

同型半胱氨酸代谢相关酶基因多态性与心肌梗死关系的研究

目的研究同型半胱氨酸代谢相关酶亚甲基四氢叶酸还原酶(MTHFR)、胱硫醚-β-合成酶(CBS)及蛋氨酸合成酶(MS)基因多态性与心肌梗死(MI)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)和聚合酶链反应(PCR)产物直接电泳技术,检测121例MI患者(患者组)和500例健康人(正常对照组)的MTHFR C677T、CBS 844 ins68和MS A2756G基因多态性。结果MTHFR C677T基因型分别为:CC野生型、CT杂合型、TT突变型。其在患者组分布频率分别为14.0%、46.3%、39.7%,T等位基因频率为62.85%,C等位基因频率为37.15%;正常对照组中为35.6%、44.0%2、0.4%,T等位基因频率为42.4%,C等位基因频率为57.6%。两组间各基因频率及等位基因频率比较差异均具有统计学意义(P<0.05)。而CBS 844ins 68和MSA2756G的基因型频率分布,两组间差异均无统计学意义(P>0.05)。结论MTHFR基因TT基因型,T等位基因与MI具有相关性;而CBS 844 ins68及MS A2756G基因多态性可能与MI发生无直接相关性。     

载脂蛋白B基因多态性与心肌梗死的关系

目的研究载脂蛋白B(apoB)基因多态性与心肌梗死发病的关系.方法用聚合酶链反应(PCR)法对65例心肌梗死(MI)患者和60例正常人apoB基因XbaI和MspI两个酶切位点上限制性片段长度多态性(RFLPs)进行检测.结果MI组Xbal酶切位点上X+等位基因频率显著高于对照组,分别为0.092和0.025(P<0.05).MspI酶切点位上M-等位基因相对频率在MI组和对照组之间无明显差异.结论XbaIRFLPs可以作为MI的独立预测指标.     

脂联素基因单核苷酸多态性与急性心肌梗死的相关性研究

目的研究脂联素基因单核苷酸多态性（SNP）与急性心肌梗死（AMI）的相关关系。方法采用聚合酶链反应-限制性片段长度多态法（PCR-RFLP）检测78例AMI患者和84例健康正常对照者脂联素基因外显子2 SNP＋45和内含子3 SNP＋276基因型,分别比较2组基因型分布和等位基因频率。结果 AMI组中脂联素基因SNP＋276为GT基因型者明显高于对照组（P〈0.05）,而等位基因频率未见显著性差异;脂联素基因SNP＋45基因型分布和等位基因频率2组间未见显著性差异。AMI组中脂联素基因SNP＋276为GG＋GT基因型者血糖浓度显著高于TT基因型者（P〈0.05）;AMI组脂联素基因SNP＋45为GG基因型者胆固醇浓度高于TT和TG基因型者（P〈0.05）。结论脂联素基因SNP＋276与AMI有相关关系,GT基因型者具有急性心肌梗死高易感性;脂联素基因外显子SNP＋45和内含子SNP＋276基因多态性可能分别与AMI高危因素胆固醇和血糖浓度有关。     

Intracardiac renin-angiotensin system and myocardial repair/remodeling following infarction

The circulating renin-angiotensin system (RAS) is a classic endocrine system that regulates cardiovascular homeostasis during physiologic and pathologic states. Accumulated evidence has shown the presence of components of RAS in various tissues, which are upregulated in certain pathological conditions. Locally produced angiotensin (Ang)II may play an important role in tissue repair/remodeling in autocrine and/or paracrine manners. Following acute myocardial infarction (MI), cardiac repair occurs in the infarcted myocardium and structural remodeling is developed in noninfarcted myocardium, which are accompanied by activated cardiac RAS. In this review, the current understanding of independent activation of cardiac RAS and its regulation in the pathogenesis of myocardial repair/remodeling after MI is discussed.     

Prothrombotic gene polymorphisms and plasma factors in young north Indian survivors of acute myocardial infarction

The aim of this study was to evaluate the association of prothrombotic gene polymorphisms [factor V Leiden (FVL) 1691GA, factor VII (FVII) 10976GA, FVII HVR4, platelet membrane glycoproteins GP1BA 1018CT, GP1BA VNTR, integrin ITGB3 1565TC, integrin ITGA2 807CT and methylenetetrahydrofolate reductase (MTHFR) 677C/T], plasma factors (fibrinogen and homocysteine) and traditional risk factors with acute myocardial infarction (AMI) in 184 patients ≤ 40 years of age and 350 controls (≤ 40 years) from north India. Multiple logistic-regression analysis showed that hypertension (OR 1.9, 95 % CI 1.1-3.8, p = 0.042), diabetes mellitus (OR 10.5, 95 % CI 2.0-56.7, p = 0.006), smoking (OR 7.1, 95 % CI 3.7-13.6, p < 0.001), low socio-economic status (OR 13.5, 95 % CI 2.3-78.4, p = 0.004), high waist-hip ratio (OR 35.6, 95 % CI 11.1-53.7, p < 0.001) and FVL 1691GA (OR 6.0, 95 % CI 1.2-13.4, p = 0.03) were independent risk predictors of AMI in young. Elevated plasma fibrinogen also showed association with increased AMI risk. ITGA2 807C/T polymorphism showed protection against AMI in univariate analysis only, while GP1BA VNTR-ac (OR 0.4, 95 % CI 0.2-0.9, p = 0.033) showed significant protection even after adjusting for age and sex. Multinominal logistic-regression analysis showed gene-gene (GP1BA 1018C/T with GP1BA VNTR and ITGA2 807C/T with ITGB3 1565T/C polymorphisms) and gene-environment interactions (gene polymorphisms with smoking) operating in the occurrence of AMI in young. In conclusion, the role of inherited predisposition to thrombosis in complex, polygenic and multifactorial disease like AMI is limited to certain genetic factors, in combination with environmental factor like smoking.     

肾素-血管紧张素系统基因多态性与高血压病患者伊贝沙坦降压幅度关系的研究

目的：对原发性高血压患者采用血管紧张素Ⅱ受体拮抗剂（伊贝沙坦）单药治疗，在观察降压疗效的同时测定RAS基因多态性靶位点：ACEI／D、ACTM235T、AT1R 1166A／C、573T／C、1062A／G、-521C／T的基因型，旨在发现与血管紧张素Ⅱ受体拮抗剂降压疗效相关的基因多态性位点。方法：符合WHO／ISH高血压诊断标准轻、中度高血压患者117例，服用伊贝沙坦单药治疗8周，在临床观察疗效的同时，应用RFLP及PCR的方法对患者血白细胞基因组DNA进行RAS基因多态性位点ACEI／D、AGT M235T、AT1R 1166A／C、573T／C、1062A／G、-521C／T基因型的分析。结果：含ACED等位基因、的患者服用伊贝沙坦后SBP下降幅度明显大于Ⅱ型基因型患者，两者之间有统计学差异（P〈0．05）；含AT1R 573T等位基因的患者服用伊贝沙坦后收缩压下降幅度明显大于CC纯合基因型患者，两者之间有统计学差异（P〈0．05）；AGT M235T、AT1R 1166A／C、-521C／T各基因型之间BP下降幅度均无显著差异。所有入选患者未发现AT1R 1062A→G的变异。结论：肾素-血管紧张素系统基因多态性位点ACEI／D及AT1R 573T／C与ARB类药物的药物敏感性有一定相关性。     

肾素-血管紧张素系统基因多态性与冠心病合并慢性心力衰竭严重程度的关系

目的检测部分中国南方汉族人群冠心病合并慢性心力衰竭患者的ACE及AGT基因多态性分布情况,以探讨肾素-血管紧张素系统（1／AS）基因多态性对冠心病合并慢性心力衰竭严重程度的影响。方法应用聚合酶链反应及限制性片断长度多态性技术,对210例冠心病合并慢性心力衰竭患者的ACE基因插入／缺失（I/D）及AGT基因M235T多态性进行检测,采用彩色多普勒检测患者的左室舒张末内径（LVDD）及左室射血分数（LVEF）。结果不同ACE基因型患者其LVDD及LVEF均存在差异,LVDD（DD）〉LVDD（ID）〉LVDD（II）（P〈0．05）,LVEF（DD）〈IXEF（ID）〈LVEF（II）（P〈0．05）,不同AGT基因型亚组间LVDD及LVEF差别均无统计学意义（P〉0．05）。结论ACE基因I／D多态性与中国南方部分汉族人群冠心病合并慢性心力衰竭的严重程度相关,DD型ACE基因的冠心病患者发生心力衰竭后病情较其他基因型者更加严重。AGT基因M235T多态性似与冠心病合并慢性心力衰竭的严重程度无关。     

Association of platelet collagen receptor polymorphisms with premature acute myocardial infarction

The impact of platelet collagen receptor polymorphisms in the pathogenesis of myocardial infarction at young age remains unknown. To determine whether either of the two platelet collagen receptor polymorphisms (GP VI T13254C and GP Ia C807T) was associated with premature acute myocardial infarction. One hundred patients with premature acute myocardial infarction and 100 age-matched controls with normal coronary angiograms were studied. Genotyping was done using PCR followed by restriction fragment length polymorphism (RFLP). GP Ia C807T polymorphism was more frequent in the patient group (65%) than in the control group (53%). However, there was no association between this polymorphism and premature acute myocardial infarction (P?=?0.08). The prevalence of T13254C polymorphism did not differ between patients (38%) and controls (33%), and this polymorphism was not associated with premature acute myocardial infarction (P?=?0.46). Logistic regression analysis also indicated no association between these polymorphisms and premature acute myocardial infarction (C807T with P?=?0.51 and T13254C with P?=?0.20). There is no association between GP VI T13254C or GP Ia C807T polymorphisms and premature acute myocardial infarction.     

血尿酸与代谢危险因素交互作用对高血压的影响

探讨血尿酸与高血压的关系,评估代谢危险因素与血尿酸交互作用对高血压风险的影响.检测8 415名健康体检人群的血压及其他相关指标,进行统计分析.高血压风险随血尿酸水平的升高而增加(P＜0.01).血尿酸与年龄、高密度脂蛋白胆固醇(HDL-C)交互作用对高血压风险的影响有统计学意义(交互作用P值分别为0.012,0.001).血尿酸水平与高血压风险有关,年龄和HDL-C水平可能影响这种联系.

Abstract：

The relationship between serum uric acid(SUA) and hypertension was investigated and the interactions of SUA with metabolic risk factors was assessed. Blood pressure and biomarkers features were evaluated for all the8 415 individuals from a community-based health examination survey in Xuzhou, and the statistical analysis was made. Raised blood pressure was associated with increased SUA concentration(P＜0.01). Age and high density lipoprotein cholesterol(HDL-C) significantly interacted with SUA(P for interaction=0.012 and 0.001, respectively). There is significant association between SUA and hypertension, which may be affected by age and HDL-C levels.     

Relationship between gene polymorphisms and prevalence of myocardial infarction among diabetic and non-diabetic subjects

This study was aimed to examine cholesteryl ester transfer protein (CETP), apolipoprotein AI and CIII gene polymorphisms, and to verify whether these genetic determinants are associated with the prevalence of myocardial infarction (MI) or type 2 diabetes. The TaqIB restriction fragment length polymorphism (RFLP) in intron I of the CETP gene, the MspI in the third intron of the APOAI gene, and also SstI in the 3' untranslated region of the APOCIII gene were determined using standard methods. The prevalence of these polymorphisms was compared between diabetic (n = 119), and non-diabetic (n = 100) middle-aged individuals of both sexes. We found a higher prevalence of the B2B2 genotype of the CETP gene among diabetics than that observed in non-diabetics (P < 0.05), and a lower prevalence of this genotype among patients with previous MI (P < 0.02). The MspI polymorphisms of the APOAI gene showed that M1++ genotype was found mainly in diabetic patients (P < 0.04). Conversely, the SstI polymorphism of APOCIII gene was not significantly associated with either MI or diabetes. Therefore, among these genetic polymorphisms, TaqIB of CETP and MspI of apolipoprotein AI appeared to help significantly to identify diabetic individuals. In particular, the former may have an additional role in the primary prevention of coronary disease.