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.     

白细胞介素-35基因多态性与冠心病患者认知功能障碍的相关性研究

目的 探讨白细胞介素（IL）-35基因多态性与冠心病患者认知功能障碍发生风险的相关性。方法 选择2015年2月—2016年10月在广西壮族自治区人民医院心血管内科首次诊断为冠心病的患者349例,均使用简易精神状态检查量表（MMSE）进行认知功能评估,按评估结果分为认知功能正常组（对照组）205例和认知功能损伤组（病例组）144例。使用Sequenom Mass Array系统对IL-35单核苷酸多态性（SNPs）位点（rs582054、rs2243115、rs428253、rs583911、rs568408和rs4740）进行基因型分析。使用酶联免疫吸附实验（ELISA）检测血浆IL-35水平。其他相关指标均由广西壮族自治区人民医院检验科按标准流程进行检测。采用Logistic回归模型探讨IL-35 SNPs与冠心病患者认知功能障碍发生风险的相关性。结果 2 组间血浆 IL-35 水平差异无统计学意义［42.26（17.19,203.06）ng/L vs.40.60（22.69,105.65）ng/L,Z=0.384,P＞0.05］。Logistic 回归分析结果显示,校正吸烟史、饮酒史、高血压、糖尿病病史、认知功能障碍家族史、年龄、丙氨酸转氨酶（ALT）及空腹血糖水平等因素后,并未发现 IL-35 多态性位点（rs582054、rs2243115、rs428253、rs583911、rs568408和rs4740）与冠心病患者认知功能障碍发生风险存在相关性。结论 IL-35基因SNPs与冠心病患者认知功能障碍发生风险之间不存在相关性,将来仍需进一步扩大样本量并对其可能的机制进行探讨。     

Association of serum omentin-1 levels with coronary artery disease

Aim:

Omentin-1, a novel adipokine expressed in visceral adipose tissue, is negatively correlated with insulin resistance and obesity. Decreased omentin-1 expression has been found in many chronic inflammatory diseases. However, the role of omentin-1 in coronary artery disease (CAD) has not been elucidated. The aim of the present study was to determine whether serum concentration of omentin-1 was independently associated with CAD.

Methods:

One hundred and fifty five patients with CAD were divided into two groups: acute coronary syndrome (ACS) and stable angina pectoris (SAP). A total of 52 healthy participants served as controls. Serum concentrations of omentin-1 and interleukin-6 (IL-6) were measured using ELISA. The association of omentin-1 with CAD and cardiovascular disease risk factors was evaluated.

Results:

Serum omentin-1 levels were lower in patients with ACS or SAP compared with controls (ACS, 113.08±61.43 ng/mL; SAP, 155.41±66.89 ng/mL; control, 254.00±72.9 ng/mL; P<0.01). Patients with ACS also had lower serum concentrations of omentin-1 compared with patients with SAP (P<0.01). Serum concentration of omentin-1 was negatively correlated with body mass index (r=−0.17, P<0.05) and serum IL-6 concentration (r=−0.19, P<0.05). Furthermore, multiple logistic regression analysis showed that serum omentin-1 concentrations were independently correlated with CAD.

Conclusion:

The findings suggest that serum concentrations of omentin-1 are related to CAD.     

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。     

转化生长因子-β1基因多态性与冠心病的相关性研究

目的探讨转化生长因子-β1（TGF-β1）基因多态性与冠心病的相关性。方法采用聚和酶链反应一限制性片断长度多态性（PCR—RFLP）技术,检测300例冠心病患者（冠心病组）及300例健康人（对照组）-509C／T位点的TGF-β1的基因多态性,同时检测血清血脂和超敏C反应蛋白（hsCRP）水平。结果冠心病组血清超敏C反应蛋白、总胆固醇、低密度脂蛋白胆固醇、载脂蛋白B水平和C、T等位基因频率明显大于对照组,差异有统计学意义（P〈0．01,P〈0．05）。结论TGF-β1基因-509C／T基因多态性与冠心病的发病有相关性;C等位基因可能是冠心病发病的易感基因。     

Association between periodontal disease and coronary artery disease

The etiology of coronary artery disease (CAD) is multifunctional. There is increasing evidence that dental infections could play a role in the initiation and development of CAD. In a case control double blind study, one hundred male and female (mean age 51 ± 9.4) angiographically documented CAD, compared with one hundred male and female patients (mean age 50.6 ± 9) with angiographically negative coronary artery. All the patients (cases and control) underwent dental examination for the presence and severity of periodontitis by a dentist who was oblivious the result of the angiography performed. The association between periodontal disease status and CAD was significant (P=0.011); periodontitis was apparently more frequent in CAD positive patients than in control (86% versus 61%). Adjustment of coronary risk factors (smoking, DM, hypertension and hyperlipidemia) in both cases and control groups suggests that the association between periodontitis and CAD in our study was independent of coronary risk factors. There is increasing evidence that dental infection, especially aerobic organisms which have capability of aggregation of platelets, is the most important cause. Dental infection would be an independent risk factor for CAD.     

载脂蛋白M的基因多态性与冠心病的相关性

目的 探讨载脂蛋白M(ApoM)的基因多态性与冠心病的相关性.方法 以聚合酶链反应-限制性内切酶片段多态性分析(PCR-RFLP)方法 检测冠心病组(118例)和对照组(非冠心病患者225例)ApoM的基因多态性,以酶法测定血浆中脂质.结果 与对照组相比,冠心病组ApoM基因-778位点等位基因C的频率增高(P＜0.01).多参数回归分析提示,基因型CC CT的优势比(OR)为1.9(95% CI=1.1～2.9, P＜0.01),等位基因C的OR为1.9(95% CI=1.3～3.2, P＜0.01).基因型CC CT的研究人群中血清总胆固醇的水平明显高于TT基因型的人群.结论 ApoM基因-778位点等位基因C是冠心病的危险因子,而且C等位基因与血清胆固醇相关.     

ORAI1基因rs3741596单核苷酸多态性与川崎病的关系

摘要： 目的 探讨钙释放激活钙调节蛋白1 （CRACM1/ORAI1） 基因rs3741596位点单核苷酸多态性 （SNP） 与川崎病 （KD） 易感性及KD并发冠状动脉病变 （CALs） 是否相关。方法 将确诊的46例KD患儿 （病例组） 和25例健康儿童（对照组） 纳入本研究, 并根据是否出现CALs将病例组分为CAL组 （20例） 和无CAL （NCAL） 组 （26例）。应用聚合酶链反应 （PCR） 技术联合基因直接测序技术检测所有研究对象ORAI1基因rs3741596位点SNP, 并进行统计学分析。结果 所有研究对象均检测到ORAI1基因rs3741596位点SNP, 其基因型分布及等位基因频率在病例组及对照组间差异无统计学意义 （χ2 分别为0.712和0.499, 均P＞0.05）, 而在CAL组和NCAL组间差异有统计学意义 （χ2 分别为 6.524 和 6.891, 均 P＜0.05）; 携带 G 等位基因使 KD 患儿并发生 CALs 的危险性增加（OR=5.444, 95%CI： 1.386~ 21.380）。结论 ORAI1基因rs3741596位点SNP可能与KD易感性无相关性, 但与KD并发CALs易感性相关。     

Selective agonists reveal alpha(1A)- and alpha(1B)-adrenoceptor subtypes in caudal artery of the young rat

Multiple alpha(1)-adrenoceptors were evaluated in caudal artery of the young Wistar rat using selective agonists and antagonists. Arteries were exposed to the selective alpha(1A)-adrenoceptor agonist, A-61603 (N-[5-(4,5-dihydro-1H-imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl] methanesulfonamide) or to phenylephrine and to prazosin (alpha(1)-adrenoceptor antagonist), or the selective alpha(1A)-adrenoceptor antagonists 5-methylurapidil, RS 100329 (5-methyl-3-[3-[4-[2-(2,2,2,-trifluoroethoxy)phenyl]-1-piperazinyl]propyl]-2,4-(1H)-pyrimidinedione), RS 17053 (N-[2(2-cyclopropylmethoxy) ethyl]-5-chloro-alpha, alpha-dimethyl-1H-indole-3-ethanamide), and the selective alpha(1D)-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5] decane-7,9-dione). Results showed a 100-fold higher potency of A-61603 for the alpha(1)-adrenoceptor present in the artery, compared with phenylephrine. Prazosin displaced both agonists with high affinity, whereas 5-methylurapidil, RS 100329 and RS 17053 displaced A-61603 with high affinity, indicating the presence of alpha(1A)-adrenoceptors. The selective alpha(1A)-adrenoceptor antagonists blocked phenylephrine responses with low affinity, suggesting that phenylephrine activated a second receptor population in caudal artery. BMY 7378 antagonized with low affinity both A-61603 and phenylephrine-induced contractions, indicating absence of alpha(1D)-adrenoceptors in the vessel. The results suggest that functional alpha(1B)-adrenoceptors are present in caudal arteries of the young Wistar rat.     

Identification of new single-nucleotide polymorphisms in the thrombin receptor gene and their effects on coronary artery diseases in Koreans

1. The thrombin receptor (the protease-activated receptor-1; PAR-1) is located on vascular cells as well as platelets and may play important roles in atherosclerotic disorders, such as coronary artery diseases (CAD). In the present study, we searched for genetic polymorphisms of the PAR-1 gene and evaluated their effects on CAD by association analysis. 2. We identified six polymorphisms in the 5'-untranslated region of the PAR-1 gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP); five single-nucleotide polymorphisms (SNP) at -2355 (A to G), -2333 (T to G), -1428 (G to A), -1071 (C to T) and -561 (A to G) and a simple sequence repeat (SSR) polymorphism between -1935 and -1841. Five SNP were in strong linkage disequilibrium with each other to make three major haplotypes, the frequency of which was over 90% of all possible haplotypes. 3. For association analysis, 150 patients who had CAD (CAD+), 58 subjects who had no stenosis on the coronary angiogram and 186 reference subjects who had no clinical evidence of CAD were used from the Korean population. The genotype frequencies of the SNP were in Hardy-Weinberg equilibrium, except A-561G in CAD+. The association of these SNP as well as of the SSR with CAD was not evident. This result suggests no major roles of the PAR-1 gene in CAD in Koreans.     

冠心病基因多态性的研究进展

冠心病是一种由环境和遗传因素共同作用所引起的复杂性多基因遗传病,掌握其发病机制,对冠心病的诊疗至关重要。随着单核苷酸多态性研究和全基因组关联研究的迅速发展,人们对冠心病基因学的研究更加深入,并发现了多个候选基因。现对近几年冠心病相关的热点基因多态性研究成果予以综述。     

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.     

颈动脉粥样硬化与冠心病的相关性研究

目的：探讨颈动脉粥样硬化和冠心病之间的关系。方法：对42例疑似冠心病的患者同时作颈动脉超声和冠脉造影检壹。结果：30例冠脉造影阳性,其中25例颈动脉超声发现粥样斑块。结论：无创性的颈动脉超声检测可以间接反映冠心病。     

中国汉族健康人群细胞色素P450 2S1的基因多态性研究

目的探索中国汉族健康人群细胞色素P4502S1(CYP2S1)基因多态性及其单倍型的分布。方法用基质辅助激光解吸电离飞行时间质谱技术(MALDI-TOF-MS)对204例无直接血缘关系的中国汉族健康受试者进行CYP2S1基因多态性检测,并用Phase 2.1软件分析单倍型的分布频率。结果 rs184623、rs338583、rs338598、rs338600在中国汉族健康人群的分布频率分别为21.3%,21.2%,55.5%,23.0%;TTGA、TTTA、CCTA、TTTG单倍型的分布频率分别为37.3%,26.1%,10.2%,8.8%。结论 rs184623、rs338583、rs338598、rs338600在中国汉族健康人群中的分布频率较高,TTGA单倍型分布频率最高。     

中国汉族冠心病患者ABCB1 C3435T多态性与氯吡格雷抗血小板作用相关性的Meta分析

目的:系统评价中国汉族冠心病患者ABCB1 C3435T多态性与氯吡格雷抗血小板作用相关性。方法:计算机检索PubMed、CBM、CNKI、VIP和WanFang Date数据库,纳入关于中国汉族冠心病患者ABCB1 C3435T多态性与氯吡格雷抗血小板作用相关性的研究,检索时限均为建库至2015年3月。由2名研究者按纳入与排除标准独立筛选文献、提取资料并评价纳入研究的方法学质量后,采用RenMan 5.3软件进行Meta分析。结果:共纳入6篇文献,包括4024例患者。研究结果显示:中国汉族冠心病患者ABCB1 C3435T多态性与血小板活性相关[CT+CC vs.TT:OR=1.66,95%CI(1.21,2.29),P=0.002;TT vs.CC:OR=0.60,95%CI(0.43,0.85),P=0.004;T vs.C:OR=0.79,95%CI(0.66,0.93),P=0.02];ABCB1 C3435T多态性与主要不良心脏事件(MACE)及出血发生无显著相关性。结论:携带ABCB13435C等位基因的中国汉族冠心病患者服用氯吡格雷后血小板活性较TT型显著增加。     

新疆维吾尔族人群SLC22A1基因的单核苷酸多态性研究

目的：研究有机阳离子转运体SLC22A1基因单核苷酸多态性（SNP）rs2282143位点（P341L,1022C>T）基因型和等位基因在中国新疆维吾尔族人群中的分布频率,并比较其与不同种族间的分布差异。方法：通过SNaPshot SNP分型技术检测276例新疆维吾尔族健康人群的SLC22A1基因SNP rs2282143位点的基因型,并与国际人类基因组单倍型图谱计划（HapMap）中不同国家或地区就该位点的SNP分型数据进行比较,分析基因型频率和等位基因频率间的差异。结果：在新疆维吾尔族健康人群中,SLC22A1基因rs2282143位点中CC基因型最常见,分布频率为90.9%;CT和TT基因型分布频率分别为8.4%、0.7%;最小等位基因T的分布频率为4.9%。新疆维吾尔族SLC22A1基因rs2282143位点的基因型频率和等位基因频率分布与黄种人群存在显著差异;而与高加索人群和黑人不存在显著差异,其中与约鲁巴人群的基因型频率存在显著差异,但与该人群的等位基因分布频率分布不存在显著差异。结论：新疆维吾尔族人群SLC22A1基因具有显著的基因多态性,其SNP rs2282143位点基因型和等位基因的分布频率与部分国家或地区人群存在较大差异,该差异对于有机阳离子转运体SLC22A1基因相关的疾病诊断、药物基因组学以及人类进化史方面的研究可能起重要作用。     

冠心病患者冠脉严重程度与冠心病危险因素的相关性分析

目的探讨冠心病患者冠状动脉(冠脉)严重程度与冠心病危险因素的相关性。方法 80例行冠状动脉造影检查者,按病变程度分为观察组(经冠状动脉造影确诊的冠心病患者)和对照组(冠状动脉粥样硬化狭窄程度<10%的患者),各40例。回顾性分析两组患者的临床资料;分析冠心病患者及冠状动脉病变程度的相关因素。结果冠心病重度病变患者吸烟例数少于中度和轻度病变患者, 2型糖尿病、高血压例数多于轻度病变患者, LVEF异常例数少于轻度病变患者,差异具有统计学意义(P<0.05)。Logistic分析结果显示,吸烟、2型糖尿病、高血压与冠状动脉病变程度相关(P<0.05)。结论 2型糖尿病、高血压、吸烟、男性为冠心病的危险因素,且冠状动脉病变程度与患者的左心功能降低有关,由此,积极控制与冠状动脉病变关系更大的冠心病危险因素,可以早期防治冠心病进一步恶化的发生,减少冠状动脉狭窄与后期严重并发症的出现。     

杂交冠状动脉血运重建术与CABG治疗多支冠状动脉疾病中远期随访的Meta分析

目的 系统评价杂交冠状动脉血运重建术（HCR）与冠状动脉旁路移植术（CABG）治疗多支冠状动脉疾病 中远期疗效与并发症。方法 系统检索Embase、PubMed、Web of Science、Cochrane Central Registry of Controlled Trials （Central）、万方数据、中国知网,筛选符合纳入标准的文献,并计算每项研究中的比值比（odds ratio,OR）和95%置信 区间（95%CI）,采用RevMan 5.3软件进行Meta分析。结果 9篇文献纳入研究,累计研究对象4 030例,其中1 142例 接受HCR治疗,2 888例接受传统CABG治疗。Meta分析结果显示：（1）中远期随访中HCR组术后全因病死率（OR= 0.72,95%CI：0.54～0.96）和主要心脑血管事件（MACCE,OR=0.54,95%CI：0.35～0.82）均低于CABG组。而在血运重 建（OR=0.90,95%CI：0.61～1.34）及心肌梗死或心绞痛发生率（OR=0.51,95%CI：0.18～1.41）方面差异无统计学意义。 （2）中期随访中 HCR 组的 MACCE 发生率低于 CABG 组（OR=0.31,95%CI：0.15～0.66）,而全因病死率（OR=0.79, 95%CI：0.52～1.22）、血运重建（OR=0.77,95%CI：0.30～1.96）以及心肌梗死或心绞痛发生率（OR=0.71,95%CI：0.05～ 9.46）等差异无统计学意义。（3）远期随访中HCR组术后全因病死率（OR=0.67,95%CI：0.46～0.98）及心肌梗死或心绞 痛发生率（OR=0.32,95%CI：0.15～0.68）均低于 CABG 组。而在 MACCE（OR=0.72,95%CI：0.43～1.21）与血运重建 （OR=0.93,95%CI：0.60～1.45）方面差异无统计学意义。结论 HCR相比CABG可降低多支冠状动脉病变患者的中 期MACCE和远期全因病死率、心肌梗死或心绞痛发生率。     

Rosiglitazone, a peroxisome proliferator-activated receptor γ stimulant, abrogates diabetes-evoked hypertension by rectifying abnormalities in vascular reactivity

In addition to insulin sensitization, rosiglitazone exhibits favourable circulatory effects. In the present study, we tested the hypothesis that rosiglitazone protects against hypertension and vascular derangements caused by diabetes. Diabetes was induced by a single bolus injection of streptozotocin (50 mg/kg, i.p.). After 2 weeks, rats were started on a treatment regimen of 5 mg/kg rosiglitazone daily for a period of 6 weeks. The control group consisted of rats treated with vehicle (distilled water) for the same period of time. After 6 weeks treatment, blood pressure (BP) was recorded and serum levels of glucose, advanced glycation end-products (AGE), triglycerides, total cholesterol and low-density lipoprotein-cholesterol (LDL-C) were determined. In in vitro experiments, concentration-response curves were constructed to phenylephrine (PE), KCl and acetylcholine (ACh) in thoracic aorta rings. In addition, ACh-induced nitric oxide (NO) generation and KCl-induced intracellular Ca accumulation were determined in the aorta. Compared with values in control rats, both diastolic and systolic BP were increased in diabetic rats. Rosiglitazone treatment of diabetic rats abolished the increase in diastolic BP and significantly reduced the increased systolic BP without affecting the development of hyperglycaemia. The possibility that changes in vascular reactivity and/or lipid profile contributed to the effects of rosiglitazone on BP in diabetic rats was investigated. In aortic rings from diabetic rats, contractile responses to KCl were increased, whereas the relaxant responses to ACh were decreased. In rings from diabetic rosiglitazone-treated rats, the exaggerated response to KCl and the impaired response to ACh were abolished. Furthermore, rosiglitazone abrogated impaired ACh-stimulated NO generation in aortas isolated from diabetic rats. Diabetes in rats was accompanied by elevated levels of triglycerides, total cholesterol, LDL-C and AGE. Rosiglitazone treatment abrogated the increased levels of triglycerides, total cholesterol and LDL-C, but only partially reduced AGE levels. Collectively, these observations indicate that rosiglitazone abrogates diabetes-evoked hypertension by ameliorating detrimental changes in vascular reactivity and lipid profiles.