髓过氧化物酶-463G/A基因多态性与冠状动脉疾病相关性研究

目的:通过对髓过氧化物酶-463G/A基因多态性分型,探讨其与冠状动脉疾病(CAD)易患性的关系。方法:采用病例-对照研究的方法。病例组79例,均行冠状动脉造影证实患有CAD;正常对照组69例,部分行冠状动脉造影证实冠状动脉正常,部分为门诊健康体检者,正常对照组所有入选病例均排除CAD史,脑卒中短暂性脑缺血发作病史及相似病史,排除周围血管疾病史。均用PCR-RFLP的方法判断各组基因型,最后进行统计学分析。结果:携带等位基因A的CAD发病率是携带基因G的0.433倍;病例组中造影结果不同的2组比较,携带至少1个A基因的冠心病的发生是不携带该基因的0.197倍。结论:髓过氧化物酶基因-463位点G/A多态性与CAD的易患性显著相关。该位点A基因的表达在CAD的发生过程中起保护性作用。     

血尿酸不是冠心病的独立危险因素

目的探讨血尿酸浓度升高是否为冠心病的独立预测因子。方法对上海交通大学附属第六人民医院心内科2003-09~2004-03住院患者临床资料进行回顾性分析,选择经冠状动脉造影证实的连续性冠心病患者118例(稳定型心绞痛36例,不稳定型心绞痛28例,急性心肌梗死54例),年龄66(65·79±10·03)岁,其中男94例、女24例;同期冠脉造影正常的连续性入院患者67例作为对照组,年龄61(60·75±11·98)岁,其中男43例、女24例。入院第2天清晨取空腹12h抽取静脉血进行血尿酸、血脂等各种生化检查,详细询问包括吸烟、高血压等病史。入院期间行冠脉造影检查。结果冠心病组血尿酸浓度高于对照组[(372·31±100·28)mmol/L对(340·08±81·58)mmol/L,P=0·028],冠心病组之间血尿酸浓度差异并无显著性。但Logistic回归分析显示血尿酸并非冠心病的独立危险因素。结论血尿酸浓度升高可能只是动脉粥样硬化的一个标志,而非冠心病的独立危险因素。     

主动脉脉搏波传导速度升高与冠心病发病的相关性

目的:探讨脉搏波传导速度(PWV)对冠心病(CHD)的预测价值。方法:患者分为非CHD组(97例)和CHD组(114例)。比较2组患者CHD危险因素以及各动脉段PWV的差异,采用Logistic回归分析比较上述危险因素在CHD发病中的作用。结果:CHD组患者的性别构成、年龄、高血压、糖尿病、血脂异常、吸烟等显著多于非CHD组(P<0.05),CHD组踝肱指数显著低于非CHD组。CHD组患者的心-左右股动脉段PWV和心-左右桡动脉段PWV显著大于非CHD组(P<0.01),而左右股-踝动脉段PWV在CHD组和非CHD组差异无统计学意义。Logistic回归分析发现,患高血压、糖尿病、血脂异常、吸烟以及心-股动脉段PWV升高、踝肱指数降低等与CHD的发生显著相关(P<0.05)。结论:同高血压、糖尿病、血脂异常、吸烟一样,心-右股动脉段PWV显著增高以及踝肱指数降低也是CHD发病的危险因素。     

安徽地区冠心病人群冠状动脉病变特征与载脂蛋白E基因多态性的研究

目的研究安徽地区冠心病人群冠状动脉病变特征与载脂蛋白E(ApoE)基因多态性的相关性,评估其在冠心病诊疗及预防中的临床应用价值。方法收集2019年9月至2020年9月在合肥市第二人民医院心内科住院行冠状动脉造影检查的患者共199例,根据研究内容不同采用两种分组方式(分别是冠心病组和对照组,ε2、ε3和ε4组),采用PCR-荧光探针法检测ε2、ε3和ε4等位基因以及rs7412和rs429358的基因型。通过比较等位基因ε2、ε3、ε4携带者的冠状动脉病变特征,分析ApoE基因型/亚型与冠心病的发病及严重程度之间的关系。结果ε2、ε3和ε4在样本中的频率分别为13.6%、69.3%和17.1%,ApoE基因多态性与冠心病的发生有相关性(ε2:r=0.160,P<0.05;ε4:r=0.154,P<0.05);ε2、ε3和ε4组Gensini评分差异有统计学意义(P=0.026,0.013,0.001),犯罪血管狭窄程度和病变血管支数与ApoE基因多态性差异无统计学意义(ε2=0.15,ε3=0.822,ε4=0.276;ε2=0.324,ε3=0.849,ε4=0.233);犯罪血管病变类型中ε4携带者以局限性为主,差异有统计学意义(P=0.027)。结论 ApoE基因多态性与冠心病的发生具有良好的相关性,在安徽地区冠心病人群中,冠状动脉病变严重程度及犯罪血管病变类型与其相关。     

Vascular endothelial growth factor genetic variability and coronary artery disease in Brazilian population

Atherosclerosis results from a complex interaction between environment and genetic risk factors. The gene encoding vascular endothelial growth factor (VEGF) is associated with differential protein expression and has been investigated in coronary artery disease (CAD) studies. Based on this, we aimed at determining if patients with CAD are affected by polymorphisms (−2 578, −1 154, and 936) in the VEGF gene, and also if these polymorphisms are associated with the number of diseased vessels and degree of arterial obstruction. The case group was formed by 175 Caucasian patients with angiographically confirmed CAD, and the control group involved 108 Caucasian patients with normal coronary angiograms. Polymerase chain reaction (PCR) was used for genotyping. Allele frequencies for VEGF −2 578A, −1 154A, and 936T were 0.46, 0.38, and 0.14 in cases and 0.49, 0.30, and 0.13 in control subjects. Allele and genotype distribution did not significantly differ between groups. A higher frequency of the VEGF −2 578AA genotype was observed in the group with three vessel disease (P = 0.008). No association between the VEGF −2 578, −1 154, and 936 polymorphisms and degree of arterial obstruction was observed. The frequency of carriers of two copies of the haplotype AG (−2 578/−1 154) were higher in the group with three-vessel disease (P = 0.05). In summary, our report shows that the VEGF −2 578 polymorphism has an influence on CAD severity, possibly because of a reduced VEGF expression, suggesting a protective effect of VEGF in atherosclerosis.     

Paraoxonase-1 Q192R polymorphism and its association with hs-CRP and fasting blood glucose levels and risk of coronary artery disease

AimsParaoxonase-1 (PON1) has been shown to protect low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) against oxidative-modification and thereby might protect against coronary-artery-disease (CAD). Here we explored the relationship of a genetic variant (a substitution (R) Arg with (Q) Gln at position 192) of PON1 in 250 patients with/without CAD.Materials and methodsGenotyping of PON1 Q192R was carried out using Real-Time-PCR TaqMan-based-probe. Demographic-characteristics and biochemical-analyses, including fasting blood sugar (FBS), HDL, LDL, triglycerides (TG) and C-reactive protein (CRP) were evaluated. Univariate/multivariate analyses were performed to determine the association of the genetic polymorphism and CAD as well as with clinical-characteristics of population.ResultsOur findings showed that RR-genotype was more frequent in CAD-patients, compared to the wild-type genotype. Moreover, CAD patients with RR-genotype had an odd ratio of 5.0 (95% CI: 1.3–18.6; p = 0.017), versus wild-type genotype, in multivariate-analysis. Of note we also observed that CAD-patients with QQ-genotype had a significantly lower Hs-CRP level, compared to the RR-genotype.Conclusionwe demonstrate that PON1-Q192R-polymorphism was associated with CRP and FBS levels; R-allele of PON1-Q192R may be an independent risk factor for CAD. Further studies are warranted to determine the value of this marker as a surrogate marker in CAD patients.     

miR-26a-1rs7372209基因多态性与冠心病遗传易感的关系

目的研究miR-26a-1 rs7372209基因型和等位基因频率分布,探讨miR-26a-1 rs7372209基因多态性与华南地区汉族人冠心病遗传易感的关系。方法利用聚合酶链式反应-连接酶检测反应(PCR-LDR)分析技术,对295例冠心病患者和283名对照个体的miR-26a-1 rs7372209(C>T)多态位点进行分型,采用非条件逻辑回归分析统计该多态位点与冠心病易感的相关性。结果 CC、CT、TT基因型在冠心病组中的分布频率分别为54.6%、37.6%和7.8%,在对照组中分别是57.2%、37.5%和5.3%,两组间基因型频率分布差异无统计学意义(χ2=1.554,P=0.460)。携带miR-26a-1 rs7372209 T变异等位基因与冠心病的遗传易感无明显相关(OR=1.15,95%CI=0.88～1.49,P=0.315)。结论 miR-26a-1 rs7372209(C>T)多态位点与华南地区汉族人冠心病易感无相关性。     

Integration of summary data from GWAS and eQTL studies identified novel risk genes for coronary artery disease

Several genetic loci have been reported to be significantly associated with coronary artery disease (CAD) by multiple genome-wide association studies (GWAS). Nevertheless, the biological and functional effects of these genetic variants on CAD remain largely equivocal. In the current study, we performed an integrative genomics analysis by integrating large-scale GWAS data (N = 459,534) and 2 independent expression quantitative trait loci (eQTL) datasets (N = 1890) to determine whether CAD-associated risk single nucleotide polymorphisms (SNPs) exert regulatory effects on gene expression. By using Sherlock Bayesian, MAGMA gene-based, multidimensional scaling (MDS), functional enrichment, and in silico permutation analyses for independent technical and biological replications, we highlighted 4 susceptible genes (CHCHD1, TUBG1, LY6G6C, and MRPS17) associated with CAD risk. Based on the protein–protein interaction (PPI) network analysis, these 4 genes were found to interact with each other. We detected a remarkably altered co-expression pattern among these 4 genes between CAD patients and controls. In addition, 3 genes of CHCHD1 (P = .0013), TUBG1 (P = .004), and LY6G6C (P = .038) showed significantly different expressions between CAD patients and controls. Together, we provide evidence to support that these identified genes such as CHCHD1 and TUBG1 are indicative factors of CAD.     

Providing insights into atherosclerosis: A case of multivessel coronary artery disease with an anomalous straightforward vessel spared from atherosclerosis

Atherosclerotic plaques tend to involve arterial localizations in which blood flow is not laminar due to arterial bends and bifurcations. A 49-year-old man was admitted to hospital with breathlessness and was subsequently diagnosed with left ventricular failure. Coronary angiography revealed three-vessel coronary artery disease and an anomalous extra left anterior descending artery taking off from the right sinus of Valsalva and spared from atherosclerosis. The absence of side branches and the relative lack of bends in arterial geometry were considered to be the cause of resistance to atherosclerosis. The present case identifies local flow conditions as an important factor determining the genesis of atherosclerosis in arterial segments.     

男性早发性冠心病与血管紧张素原基因启动子区域-217G/A和-152G/A多态

目的:研究血管紧张素原(angiotensinogen,AGT)基因启动子区域的-217G/A和-152G/A多态与上海地区汉族男性早发性冠心病(CAD)的相关性。方法:采用多重SNaPshot反应,在100例男性早发性CAD患者和100名健康男性对照者中,对AGT基因启动子区域的-217G/A和-152G/A多态进行基因分型。结果:-217G/A多态AA、AG和GG基因型在CAD组中的分布与对照组相比有显著性差异(P=0.039),CAD组的A等位基因频率较对照组亦显著增加(P=0.012),A等位基因携带者早发性CAD的发病危险是非携带者的1.913倍(95%CI1.151～3.182)。-152G/A多态的基因型分布在2组间的差异无统计学意义(P=0.154),其A、G等位基因频率2组相比有差异(P=0.044)。在多支病变组中,-217G/A多态的基因型分布及其等位基因频率2组相比均有显著性差异(分别为P=0.010和P=0.005),且A等位基因携带者发生多支病变的危险是非携带者的2.307倍(95%CI1.274～4.179)。结论:在上海地区的汉族男性人群中,AGT基因-217G/A和-152G/A多态可能是其早发性CAD的遗传性危险因素,且-217G/A多态可能还与冠状动脉粥样硬化的病变程度相关。     

Family history as an independent risk factor of coronary artery disease.

The relationship between family history of ischaemic heart disease and the presence of coronary heart disease was studied in 387 patients undergoing routine coronary arteriography prior to valve replacement. One hundred and seven patients (27.6%) had a family history of ischaemic heart disease. Of these, 52 (48.6%) had significant coronary artery disease compared with 60 of 280 (21.4%) patients without a family history (P < 0.001). The overall severity (coronary score) and extent (number of vessels) of coronary artery disease was greater in those patients with a family history (P < 0.001). Moreover, the incidence of significant coronary disease increases as the number of relatives with ischaemic heart disease also increase (P < 0.001). Multiple logistic regression analysis suggests that family history is an independent predictor of the presence of significant coronary artery disease.     

脂联素基因SNP+276G/T单核苷酸多态性与冠心病的相关性研究

目的探讨上海汉族人群中脂联素基因多态性分布情况，研究基因多态性与冠心病的相关性。方法采用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法，以100例健康者为对照组，100例冠脉造影证实为冠心病的非糖尿病患者为冠心病组，研究脂联素基因单核苷酸多态性（SNP276G／T）与冠心病的相关性。结果冠心病组G／G基因型频率明显高于对照组，分别为29％和16％（P〈0．05），冠心病组G等位基因频率为45％，对照组为16％，冠心病组明显高于对照组（P〈0．05）；T等位基因频率冠心病组明显低于正常对照组，分别为55％和84％（P〈0．05）。相对于T／T基因型，G／G基因型修正后的OR值为3．93（P〈0．05），G／G＋G／T基因型的修正后的OR值为2．41。结论脂联素SNP＋276G／T各种基因型和冠心病的发病密切相关，G／G基因型很可能是冠心病的易感基因型。     

组织蛋白酶S基因启动子区-25G／A多态不是中国人群中冠心病的预测因子

目的这项研究的目的旨在观察中国人群中，组织蛋白酶S（CTSS）基因-25G／A多态分布及其多态性与冠心病（CAD）危险性之间的关联。方法CTSS基因-25G／A多态性由多聚酶链式反应PCR及限制性内切酶降解方法获得。经冠脉造影检查明确的共659名冠心病患者（冠脉狭窄≥50％）及352名非冠心病患者（对照组）纳入这项研究。结果所有研究对象中的等位基因G和A的频率分别为0．630及0．370。在病例组及对照组之间未发现其CTSS-25G／A多态性频率（G：0．626vs．0．633，P〉0．05；A：0．374vs．0．367，P〉0．05）及基因型分布（G：83．4VS．85．3，P〉0．05；A：58．0vs．58．5，P〉0．05）存在显著性差异。使用逻辑回归对其他危险因素校正后，CTSS基因型与冠脉狭窄严重程度之间亦未发现存在关联（P〉0．05）。结论在中国人群中，基因型AA较基因型GG和GA更为少见。对照组及冠心病组之间的等位基因频率及基因型分布均无显著性差异。CTSS-25G／A多态性与冠状动脉狭窄的发生率及严重程度不相关。     

Relook at lipoprotein (A): Independent risk factor of coronary artery disease in North Indian population

Aims

Lipoprotein (a) [Lp(a)] levels have shown wide ethnic variations. Sparse data on mean Lp(a) levels, its link with clinical variables and severity of coronary artery disease (CAD) in North Indian population needed further studies.

Methods

150 patients, each of single vessel disease (SVD), double vessel disease (DVD) and triple vessel disease (TVD) with 150 healthy controls were drawn for the study. Serum Lp(a) estimation was performed by immunoturbidimetric method.

Results

Lp(a) had a skewed distribution. Median Lp(a) level was significantly raised in cases as compared to controls (median 30.30 vs. 20 mg/dl, p < 0.001). Cases with acute coronary syndrome (ACS, 55.8%) had significantly higher median Lp(a) levels as compared to those with chronic stable angina (35.4 mg/dl vs. 23 mg/dl, p < 0.001). Significant difference in median Lp(a) levels were observed in patients with DVD or TVD versus control (30, 39.05 vs 20 mg/dl, p < 0.008). Lp(a) level was found to be an independent risk factor for CAD (AOR{adjusted odds ratio} 1.018, 95% CI 1.010–1.027; p < 0.001). Analysis using Lp(a) as categorical variable showed that progressive increase in Lp(a) concentration was associated with increased risk of CAD [AOR from lowest to highest quartile (1, 1.04, 1.43 and 2.65, p value for trend = 0.00026)]. Multivariably AOR of CAD for subjects with Lp(a) in the highest quartile (above 40 mg/dl) compared to those with Lp(a) ≤40 mg/dl was 2.308 (95% CI 1.465–3.636, p < 0.001).

Conclusion

Lp(a) above 40 mg/dl (corresponding to 75th percentile)assessed by an isoform insensitive assay is an independent risk factor for CAD. Raised Lp(a) level is also associated with increased risk of ACS and multivessel CAD.     

中国2型糖尿病人群脂联素受体1基因多态性与冠心病风险的相关性研究

目的 研究我国2型糖尿病(T2DM)人群脂联素受体1(AdipoR1)基因多态性与冠心病(CAD)风险的相关性. 方法 以307例T2DM患者为研究人群,其中205例伴有CAD,102例不伴CAD.应用聚合酶链式反应-限制性内切酶片断长度多态性(PCR-RFLP)技术或基因测序方法,研究AdipoR1 10个单倍型标记单核苷酸多态性(Haplotype-tagging SNPs)与CAD风险的关系. 结果 (1)Ad-ipoR1 SNP rs1342387 GG和AG基因型携带者均较AA型携带者发生CAD的风险显著增加(GG vsAA:校正OR'=2.491,95%CI' 1.354～6.885,P'=0.031;AG vs AA:校正OR'=3.053,95%CI' 1.085～5.718,P'=0.007).(2)SNP rs12045862基因型CC携带者与TT携带者相比,CAD的风险显著增加(校正OR'=2.751,95%CI' 1.063～7.115,P'=0.037).(3)SNPs rs1342387、rs12045862 GX/CC基因型组合携带者较非携带者CAD的风险显著增加(校正OR'=3.646,95%CI' 1.253～10.608,P'=0.018).保护性基因型组合AA/TX携带者较非携带者发生CAD的风险显著降低(校正OR'=0.260,95%CI'0.113～0.601,P'=0.002).(4)在超重和肥胖(BMI≥24)的T2DM人群中,发现肥胖与SNPs rs1342387、rs12045862对CAD的风险有相互作用(P<0.05);在总人群中发现的与CAD风险相关的SNPs rs1342387和rs12045862在这一亚组仍具有相关性;同时发现SNP rs7539542基因型CC携带者较GG携带者CAD的风险增加(校正OR'=4.714,P'=0.036). 结论 中国T2DM人群中,AdipoR1 SNPs与CAD的风险可能相关.在超重或肥胖T2DM人群中,AdipoR1 SNPs与肥胖对CAD风险的影响有协同作用.     

Association of the adiponectin rs266729 C>G variant and coronary heart disease in the low risk 'Golden Years' type 1 diabetes cohort

The C-allele of rs266729 is associated with CHD, while the G-allele of rs17300539 is associated with metabolic traits. We examined these in type 1 diabetes. For rs266729, the C-allele was associated with 8-fold increase in CHD. For rs17300539, the G-allele was associated with increases in triglycerides and waist circumference.