Background Calmodulin 1 (CALM1) mutations are involved in the development of coronary artery disease (CAD). However, the relationship of CALM1 rs3179089 polymorphism with CAD is unknown. Objective This study aimed to identify the relationship of CALM1 rs3179089 polymorphism with CAD susceptibility, CALM1 expression, blood pressure, blood glucose, blood coagulation and serum lipid levels of CAD patients. Methods 550 CAD patients and 550 control subjects were genotyped for CALM1 using Sequenom MassARRAY technology. CALM1 expression level was measured by quantitative real time polymerase chain reaction (qRT-PCR). Results CALM1 mRNA expression was higher in CAD patients than that in control subjects (P < 0.001). CAD patients with CC genotype had higher CALM1 mRNA expression level than control subjects with CC genotype (P = 0.006). Genotypic frequency of rs3179089 was different between male patients of CAD and control subjects (P = 0.045). Rs3179089 polymorphism was related to CAD risk of males in recessive model (P = 0.039). Moreover, rs3179089 polymorphism was associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), and D-Dimer (D-D) level of patients with CAD in recessive model (P = 0.013 for SBP; P = 0.034 for DBP; P = 0.004 for FPG; P = 0.046 for D-D). In addition, rs3179089 polymorphism was correlated with low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) serum levels of patients with CAD in both addictive (P = 0.025 for LDL-C; P = 0.001 for TC) and recessive models (P = 0.001 for LDL-C; P = 0.001 for TC). Conclusion CALM1 expression is associated with development of CAD. CALM1 rs3179089 polymorphism affects CAD susceptibility in males, and blood pressure, blood glucose, blood coagulation and serum lipid of CAD patients.

目的 探讨中性粒细胞弹性蛋白酶(ELANE)基因rs3761007及rs740021多态性与缺血性中风(IS)痰瘀证及其临床生物学指标的关联性.方法 纳入IS痰瘀证组和对照组各550例,运用MassARRAY SNP基因分型技术进行基因分型,RT-PCR实验技术检测基因表达水平,PLINK软件完成遗传关联分析.结果 IS痰瘀证患者的ELANE基因mRNA表达水平与对照组之间的比较未见统计学意义(P＞0.05),ELANE基因rs3761007、rs740021多态性与IS痰瘀证发生风险的关联均无统计学意义(均P＞0.05);ELANE基因rs740021多态性与IS痰瘀证患者的APO-B(隐性模型:Padj=0.007)、LDL(隐性模型:Padj=0.004)、TC(隐性模型:Padj=0.009)、APTT(隐性模型:Padj=0.034)、FIB(显性模型:Padj=0.007)、PT(隐性模型:Padj=0.015)水平显著相关,而rs3761007多态性与IS痰瘀证患者的PLT水平显著关联(隐性模型:Padj=0.033).结论 ELANE基因rs3761007及rs740021多态性可能影响IS痰瘀证的血脂代谢及凝血功能,而ELANE基因多态性可能与IS痰瘀证的风险易感性无关.

Long non-coding RNAs (lncRNAs) have been reported to play an important role in cardiovascular diseases. The present study aimed to investigate the levels of lncRNA H19 in patients with coronary artery disease (CAD) and the genetic association of lncRNA H19 rs217727 and rs4929984 polymorphisms with CAD susceptibility. We detected an upregulated expression of lncRNA H19 in the peripheral blood of CAD patients compared with healthy controls, and the area under the receiver operating characteristic curve of lncRNA H19 for CAD diagnosis was 0.918. In addition, rs4929984 was associated with the susceptibility of Han Chinese females to CAD, as shown in the additive and dominant models, and the significant association remained after adjusting for age and Bonferroni correction. The A allele carriers of rs4929984 were correlated with females' susceptibility to CAD compared with the C allele, and the A-G haplotype of rs4929984-rs217727 was associated with females' susceptibility to CAD. Furthermore, rs217727 and rs4929984 were associated with the levels of clinicopathological parameters of CAD cases. We suggest that lncRNA H19 has a potential to be a diagnostic biomarker for CAD; rs4929984 polymorphism is associated with females' susceptibility to CAD in the Han Chinese population, and lncRNA H19 variants may influence lipid metabolism, inflammation, and coagulation function of CAD patients.

目的 旨在探讨核心蛋白聚糖(decorin,DCN)基因rs7441多态性与缺血性脑卒中(ischemic stroke,IS)痰瘀证、冠心病(coronary atherosclerotic heart disease,CHD)痰瘀证的遗传关联.方法 纳入IS痰瘀证患者、CHD痰瘀证患者、对照组各550例,运用实时荧光定量PCR(qRT-PCR)方法检测DCN基因mRNA外周血表达水平,采用Sequenom MassARRAY技术进行基因分型,通过PLINK、SPSS软件进行统计分析.结果 ①DCN基因在IS痰瘀证患者、CHD痰瘀证患者外周血中的mRNA表达水平均显著低于对照组(均P＜0.001).②DCN基因外周血mRNA表达水平与IS痰瘀证患者的空腹血糖(FPG)、活化部分凝血酶原时间(APTT)、国际标准化比值(INR)、凝血酶原时间(PT)、凝血酶原时间活动度(PTA)的相关性均具有统计学意义(均P＜0.05),与CHD患者收缩压(SBP)、舒张压(DBP)也显著相关(均P＜0.050).③DCN基因rs7441多态性与IS痰瘀证、CHD痰淤证的发生风险的关联无统计学意义(均P＞0.050).④DCN基因rs7441多态性与IS痰瘀证患者的血清栽脂蛋白B(APO-B)(加性模型:Pam=0.006)、低密度脂蛋白(LDL)(加性模型:Padj=0.029)水平显著相关,rs7441多态性与CHD痰瘀证患者的国际标准化比值(INR)显著关联(加性模型:Padi=0.018).结论 DCN基因mRNA表达水平可能参与IS痰瘀证、CHD痰瘀证的发生,rs7441多态性可能影响IS痰瘀证患者的血脂代谢、CHD痰瘀证患者的凝血功能.

目的:探讨STAT5A基因rs3198502多态性位点与缺血性脑卒中痰瘀证及其血脂代谢、凝血功能、炎性反应的关联.方法:共纳入缺血性脑卒中痰瘀证患者及对照各550例,采用MassARRAY SNP技术对rs319502位点进行基因分型.以PLINK、SPSS软件进行统计分析.结果:STAT5A基因的rs319502位点与缺血性脑卒中痰瘀证发生风险的关联无统计学意义(P＞0.050).rs3198502位点与缺血性脑卒中痰瘀证患者的D-D[隐性模型:β(95％ CI)=1.85 (0.29-3.42),Padj=0.021]、INR[隐性模型:β(95％CI) =2.40(0.20-4.61),Padj=0.033]、PLT[显性模型:β(95％CI)=14.51(1.79-27.23),Padj=0.026]水平的相关性具有统计学意义.rs3198502与缺血性脑卒中痰瘀证患者的C反应蛋白水平的相关性具有统计学意义[加性模型:β(95％CI)=-7.75(-14.47--1.03),Padj=0.025;显性模型:β(95％ CI)=-9.33(-18.42--0.24),Padj=0.046].结论:STAT5A基因3198502位点可能影响缺血性脑卒中痰淤证的凝血功能、炎性反应.

目的 探讨F10基因即凝血因子X(FX)rs3093261、rs563964多态性与缺血性脑卒中(IS)痰瘀证和冠心病(CAD)痰瘀证及其凝血标志物的关联性.方法 纳入IS痰瘀证、CAD痰瘀证、对照组各550例.采用qRT-PCR技术测定外周血F10基因mRNA表达水平,运用MassARRAY SNP基因分型实验技术对F10基因rs3093261、rs563964进行基因分型.结果 IS痰瘀证、CAD痰瘀证患者的F10基因mRNA表达水平均显著高于对照组(P<0.05).F10基因rs3093261、rs563964多态性与IS痰瘀证、CAD痰瘀证发生风险的关联均无统计学差异(P>0.05).F10基因rs3093261多态性与缺血性中风痰瘀证患者的活化部分凝血酶原时间(APTT)水平显著相关(P<0.05);F10基因rs563964多态性与CAD痰瘀证患者的血小板(PLT)水平的相关性具有统计学意义(P<0.05).结论 F10基因表达水平可能影响了IS痰瘀证、CAD痰瘀证的发生,F10基因遗传多态性可能影响IS痰瘀证、CAD痰瘀证的凝血功能.

目的 探讨激酶插入结构域受体(KDR)基因多态性与缺血性中风(IS)痰瘀证、冠心病(CAD)痰瘀证及凝血功能的关联性.方法 共纳入缺血性中风痰瘀证患者550例、冠心病痰瘀证患者550例、正常对照人群550例,分为3组.采用MassARRAY SNP基因分型实验技术进行基因分型检测,使用实时荧光定量PCR(RT-PCR)方法检测外周血KDR基因mRNA表达水平,通过凝固法检测血浆中凝血功能指标.采用PLINK软件进行遗传关联分析,采用拟和优度χ2检验进行哈温平衡(HWE)分析.基因型频率分布的组间比较,采用χ2检验.应用多因素非条件Logistic回归模型对各遗传模型(加性模型、显性模型、隐性模型)与疾病的关联进行分析,采用线性回归分析各位点多态性与凝血标志物水平的关联.结果 IS痰瘀证患者的KDR基因mRNA表达水平显著低于对照组(P<0.001),而CAD痰瘀证患者的KDR基因mRNA表达水平显著高于对照组(P=0.007).KDR基因rs2305948、rs2239702多态性与IS痰瘀证、CAD痰瘀证发生风险的关联差异无统计学意义(均为P>0.05).KDR基因rs2305948多态性与IS痰瘀证患者的D二聚体(D-D)、凝血酶原时间活动度(PTA)的相关性具有统计学意义(P<0.05),KDR基因rs2239702多态性与IS痰瘀证患者的活化部分凝血酶原时间(APTT)显著相关(P<0.05).KDR基因rs2305948多态性与CAD痰瘀证患者APTT水平的相关性具有统计学意义(P<0.05),rs2239702多态性与CAD痰瘀证患者凝血酶时间(TT)水平显著相关(P<0.05).结论 KDR基因表达水平可能影响IS痰瘀证、CAD痰瘀证的发生,且KDR基因rs2305948、rs2239702遗传多态性可能影响IS痰瘀证、CAD痰瘀证的凝血功能.

A quantitative transcriptomics analysis has reported that Calmodulin 1 (CALM1) is highly expressed in human brain tissues. This study aims to evaluate the relationship between CALM1 rs3179089 polymorphism and ischemic stroke (IS) in Chinese Han population. A total of 550 patients with IS and 550 control subjects were recruited and genotyped using Sequenom MassArray technology. The mRNA expression of CALM1 was measured using quantitative real-time polymerase chain reaction. CALM1 mRNA expression was significantly higher in patients with IS than that in control subjects (P = 0.006). The genomic frequency distribution was significantly different between female patients with IS and female controls (χ2 = 6.043, P = 0.047). In recessive model, CALM1 rs3179089 polymorphism was associated with the risk of IS in female patients. GG genotype significantly increased the risk of IS compared with the CC+GC genotype in females (OR 8.68, P = 0.042; adjusted OR 8.72, Padj = 0.042). Rs3179089 polymorphism was associated positively with plasmas D-Dimer of patients with IS in recessive model (βa = 3.24, P = 0.018; βb = 3.20, Padj = 0.019). Moreover, rs3179089 polymorphism was related positively to thrombin time of patients with IS in addictive (βa = 2.32, P = 0.005, βb = 2.26, Padj=0.006) and recessive model (βa = 11.19, P = 0.001, βb = 11.13, Padj = 0.001). CALM1 expression was involved in the development of IS. CALM1 rs3179089 polymorphism was associated with IS risk in Chinese females, and related to blood coagulation of IS patients.