Haplotypes Encompassing the KIAA0391 and PSMA6 Gene Cluster Confer a Genetic Link for Myocardial Infarction and Coronary Artery Disease

The role of the KIAA0391 and PSMA6 genes in predisposing individuals to disease is still not fully understood. We evaluated by molecular beacon-based genotyping assays the roles of five single nucleotide polymorphisms (SNPs) in the chromosomal region 14q13.2 harbouring the KIAA0391 and PSMA6 gene cluster in coronary artery disease (CAD) in the Saudi population. Two of the studied SNPs rs8008319 (denoted as 1) and rs7157492 (2), reside in the KIAA0391 locus, two others rs1048990 (3) and rs12878391 (4) are components of the PSMA6 , while rs4981283 (5) resides downstream of both genes. In a study involving 1071 patients and 929 controls, none of the studied SNPs showed significant association with CAD. In contrast, two haplotypes consisting of 1A-2G-3C-4A-5A [O.R.(95% C.I.) = 1.49(0.95–2.35); p = 0.022] and 1A-2G-3G-4A-5A [2.24(0.84–5.98); p = 0.031] conferred risk for both CAD and myocardial infarction (MI) in a five-SNP locus model, while another comprising 1A-2G-3C-4A-5G [2.24(0.84–5.98); p = 0.079] showed a borderline association. One haplotype consisting of 1T-2G-3C-4G-5A [0.79(0.59–1.05); p = 0.015] exhibited protective properties and another, 1T-2G-3C-4A-5G [0.20(0.03–139); p = 0.073], showed a similar but weaker trend. Our study identified haplotypes in the chromosomal region encompassing the KIAA0391 and PSMA6 genes as a possible genetic link between CAD and MI. These results also suggest that haplotypes may be more informative than individual SNPs in identifying risk factors for disease.     

临床诊断急性心肌梗死与冠状动脉造影比较研究

目的比较冠状动脉造影(CAG)阴性和CAG阳性的急性心肌梗死(AMI)患者的临床特点。方法对临床诊断急性心肌梗死的399例患者行选择性CAG检查,并据造影结果对临床特点进行对比分析。结果CAG阳性组直径狭窄≥50%者376例,占94.24%,其中狭窄≥90%者307例(81.38%);CAG阴性组直径狭窄<50%者23例,占5.76%,其中0%狭窄7例(30.43%),10%～40%狭窄16例(69.57%)。CAG阴性组与CAG阳性组比较:小于40岁的患者26.08%(6/23)比6.12%(23/376,P<0.05);女性患者43.48%(10/23)比18.88%(71/376,P<0.05);糖尿病、高脂血症、高血压患者分别为26.08%(6/23)比15.69%(59/376),73.91%(17/23)比67.82%(255/376),26.08%(6/23)比28.48%(107/376),P均>0.05;冠心病危险因素数目无显著差异(P>0.05);左室舒张末压(LVEDP)为(12.53±5.46)mmHg比(18.75±7.10)mmHg(P<0.01);左室射血分数(LVEF)为(63.56±8.18)%比(59.56±12.04)%(P>0.05)。结论急性心肌梗死患者中CAG阴性者并非少见,主要发生机制是在冠脉内皮受损基础上冠脉痉挛或冠脉微小斑块破裂促发血栓形成,继而发生血栓自溶或溶栓干预后血栓消失。CAG阴性AMI在年轻人、女性中并不少见,心功能较好,与CAG阳性者具相同的糖尿病、高脂血症、高血压发生率。     

Lack of Association of the Vascular Endothelial Growth Factor Gene Polymorphisms with Kawasaki Disease in Taiwanese Children

INTRODUCTION: Kawasaki disease (KD) is an acute febrile vasculitis of unknown etiology that mainly occurs in infants and children. Clinical and histopathologic findings suggest that vascular endothelial growth factor (VEGF) is involved in the coronary artery lesions (CALs) development in KD. This study hypothesized that specific VEGF gene polymorphisms and their haplotypes are associated with KD susceptibility and CAL development in Taiwanese children. SUBJECTS AND METHODS: The VEGF -2578 A/C, -634 G/C, and +936 C/T single-nucleotide polymorphisms (SNPs) were genotyped in 156 children with KD and 672 ethnically matched healthy controls using the Pre-Developed TaqMan Allelic Discrimination Assay. RESULTS: No significant differences in genotype, allele, carrier, and haplotype frequencies of the three SNPs were found between healthy controls and children with KD or between patients with and without CAL. CONCLUSION: Our data suggest that VEGF -2578 A/C, -634 G/C, and +936 C/T SNPs do not confer increased susceptibility to KD or to CAL development.     

Association of SNP rs17465637 on chromosome 1q41 and rs599839 on 1p13.3 with myocardial infarction in an American caucasian population

Recent genome-wide single nucleotide polymorphism (SNP) association studies (GWAS) have identified a number of SNPs that were significantly associated with coronary artery disease and myocardial infarction (MI). However, many independent replication studies in other populations are needed to unequivocally confirm the GWAS association. To assess GWAS association, we have established a case-control cohort consisting of 1231 well-characterised MI patients and 560 controls without detectable coronary stenosis, all selected from the Cleveland Genebank population. The Genebank cohort has sufficient power to detect the association between MI and four GWAS SNPs, including rs17465637 within the MIA3 gene, rs2943634 (intergenic), rs6922269 in MTHFD1L, and rs599839 near SORT1. SNPs were genotyped by TaqMan assays and follow-up multivariate logistic regression analysis with incorporation of significant covariates showed significant association with MI for MIA3 SNP rs17465637 (P-adj= 0.0034) and SORT1 SNP rs599839 (P-adj= 0.009). The minor allele G of rs599839 was also associated with a decreased LDL-C level of 5-9 mg/dL per allele, but not with HDL-C or triglyceride levels. No association for MI or lipid levels was found for SNPs rs2943634 and rs6922269 (P-adj > 0.05). Our results establish two SNPs, rs17465637 in MIA3 and rs599839 near SORT1 as significant risk factors for MI in the American Genebank Caucasian population.     

老年急性心肌梗死并心源性休克冠状动脉 介入治疗的临床效果研究

目的 探讨冠状动脉介入治疗老年急性心肌梗死并心源性休克的临床价值。方法 回顾性分析2013年7月~2017年11月在我院接受治疗的155例老年急性心肌梗死并心源性休克患者的临床资料,根据治疗方式分为溶栓组（80例）与介入治疗组（75例）。比较两组患者尿量、心率、左心室射血分数（LVEF）以及血管开通率。结果 治疗后,介入组尿量多于溶栓组,HR值低于溶栓组,差异有统计学意义（P＜0.05）;住院前及出院6个月后,介入组LVEF值均高于溶栓组,差异有统计学意义（P＜0.05）;溶栓组出院6个月后,LVEF值高于出院前,差异有统计学意义（P＜0.05）;介入组出院前后LVEF值对比,差异无统计学意义（P＞0.05）;介入组血管开通率为93.33%,高于溶栓组的77.50%,差异有统计学意义（P＜0.05）。结论 冠状动脉介入为治疗老年急性心肌梗死并心源性休克患者的有效手段,可有效改善血液流变学、尿量,利于心功能恢复。     

Four SNPS on Chromosome 9p21 Confer Risk to Premature, Familial CAD and MI in an American Caucasian Population (GeneQuest)

Genome-wide association studies have separately identified four single nucleotide polymorphisms (SNPs) on chromosome 9p21 that confer susceptibility to coronary artery disease (CAD) and myocardial infarction (MI). This study presents the first analysis of these SNPs (rs10757274, rs2383206, rs2383207, and rs10757278) in a premature, familial CAD/MI population (GeneQuest). We performed a case-control analysis of the GeneQuest Caucasian population with 310 cases with premature CAD and MI (average age at onset of 40.3 ± 5.1) and 560 non-CAD controls to determine if these SNPs are associated with risk of CAD using both the population-based and family-based association study designs. The four SNPs are significantly associated with premature and familial MI and CAD in the GeneQuest Caucasian population (allelic P = 6.61 × 10⁻⁷ to 1.87 × 10⁻⁸). Sib-TDT analysis showed that three of the four SNPs could confer significant susceptibility to premature CAD and MI. These results indicate that the four SNPs on chromosome 9p21 are also associated with premature, familial CAD.     

红细胞压积变化对急性ST段抬高型心肌梗死患者临床预后的影响

目的 探讨红细胞压积的变化对急性ST段抬高型心肌梗死（STEMI）接受急诊经皮冠状动脉支架植入术患者的临床预后的影响。方法 连续性纳入我院心肌梗死绿色通道收治行急诊支架植入患者603例,根据住院期间红细胞压积的变化分为A组（红细胞压积降低组,255例）和B组（红细胞压积升高组,348例）。收集两组患者资本资料、手术相关信息、化验室资料、住院期间临床事件、1个月内临床事件以及1年内临床事件并予以统计分析。结果 A组年龄大于B组[（60.33±11.06）岁 vs（58.44±10.88）岁,P＜0.05],B组脑血管病史发生率高与A组（13.50% vs 8.24%,P＜0.05）,A组梗死相关动脉中血栓病变发发生率高于B组（97.25% vs 88.51%,P＜0.05）。支架植入后最终TIMI血流:3级血流A组较B组高（85.88% vs 79.02%,P＜0.05）。A组较B组住院期间心源性死亡发生率低（0 vs 2.01%,P＜0.05）;出院1年内LVEF低于B组[（55.53±6.42）% vs （57.19±6.82）%,P＜0.05];出院1年室壁运动异常发生率高于B组（92.88% vs 87.69%,P＜0.05）。结论 住院期间红细胞压积升高增加STEMI患者在院期间心源性死亡的发生,红细胞压积降低预示着心功能的下降及室壁运动功能受损。     

载脂蛋白A5基因-1131T>C多态性与冠心病易感性的关联研究

目的探讨载脂蛋白A5(apoA5)-1131T>C单核苷酸多态性与冠心病(CAD)发病风险之间的关系。方法经冠状动脉造影确诊的江苏地区冠心病患者235例,同一地区正常对照262名,采用PCRRFLP分析对apoA5基因的-1131T>C多态进行检测,比较不同基因型与个体血脂水平和冠心病患病风险的关系。结果-1131T>C单核苷酸多态位点等位基因T、C频率在CAD组和正常对照组中分别为59.57%、40.43%和65.65%、34.35%。CAD组中C等位基因的频率高于对照组(P<0.05)。与-1131TT基因型者比较,CC基因型者的冠心病患病风险显著增加(OR=1.872,95%CI=1.039-3.376,P=0.037),用Logistic回归模型对个体的年龄、性别、体重指数和抽烟、高血压等因素后,其患病风险仍明显增加(OR=2.285,95%CI=1.222-4.274)。对照组中不同基因型个体血浆甘油三酯水平差异有统计学意义(P=0.007),携带C等位基因的个体TG水平显著高于TT基因型个体。结论apoA5基因-1131T>C多态性C等位基因是中国人群中冠心病发病的危险因素之一,且与血浆TG水平的变化密切相关。     

心肌梗死临床诊断中血清肌酸激酶B亚基含量的动态变化

目的 :为提高心肌梗死的早期诊断水平 ,本文探讨用脑肌酸激酶单克隆抗体酶联免疫吸附法对血清肌酸激酶B亚基含量进行测定。方法 :用BCK McAbELISA法测定B亚基含量 ,动力学法测定CK、CK MB的活性 ,并对结果进行动态观测及比较。结果 :血清CK B亚基含量在心肌梗死急性发作期为 344 .89± 2 0 5 .18ng/ 5 0 μl;正常对照组和缓解期B亚基分别为 6 .5× 10 - 1 ± 2 .2× 10 - 4 ng/ 5 0 μl和 18.5 0× 10 - 4 ± 12 .2 0× 10 - 4 ng/ 5 0 μl。血清B亚基在心肌梗死急性发作期、缓解期、对照组中含量变化有显著性差异 (P <0 .0 5 )。结论 :BCK McAbELISA法可检测血清中微量B亚基。当心肌梗死急性发作 ,CK、CK MB尚在正常范围时 ,B亚基含量已明显升高。使用本法测定血清B亚基含量具有准确、快速、灵敏、可靠、特异性高等特点 ,为临床上早期诊断急性心肌梗死和疗效判断提供较好的方法     

Haplotype Analysis of the Stromelysin-1 (MMP3) and Gelatinase B (MMP9) Genes in Relation to Coronary Heart Disease

The functional genetic polymorphisms present in the promoters of stromelysin-1 ( MMP3 ) and gelatinase B ( MMP9 ) have been shown to be associated with angiographically measured atherosclerosis; however, haplotype analysis of the genetic polymorphisms occurring in the promoters and coding regions of MMP3 and MMP9 has been infrequently performed in the past. The aim of this study was to analyze the occurrence of the -1612 5A/6A , -376C/G , and Glu45Lys polymorphisms of MMP3 and the -1562C/T and R279Q polymorphisms of MMP9 and their relation to the risk of coronary heart disease (CHD; stenosis ≥50% of the diameter in at least one major coronary artery) in a Chinese Han population. The present study involved 1373 patients with CHD and 695 healthy controls. The Glu45Lys polymorphism of MMP3 was significantly associated with an increased risk of CHD. Compared with the 45Glu homozygotes, 45Lys allele carriers had a significantly elevated risk of CHD (adjusted OR = 1.50; 95%CI 1.11–2.03; p = 0.008). Moreover, haplotype analysis identified both the 6A-C-Lys (-1612 6A, -376C, 45Lys) haplotype and the 6A-G-Lys (-1612 6A,-376G, 45Lys) haplotype of MMP3 as associated with an increased risk of CHD. Our study suggests that common genetic variations in the MMP3 gene may affect the risk of CHD in the Chinese population.     

Association between lipoprotein-associated phospholipase A2 gene polymorphism and coronary artery disease in the Chinese Han population

The role of the lipoprotein-associated phospholipase A(2) gene (PLA2G7) in atherosclerosis remains controversial. We investigated the frequency of single-nucleotide polymorphisms (SNPs) of PLA2G7 (rs16874954 and rs1051931) and their association with coronary artery disease (CAD) in a cohort of CAD patients (n= 806) and age-matched healthy controls (n= 482) in the Chinese Han population. The VF and FF genotype of rs16874954 was significantly more frequent in the CAD patients (13.5%) than in the controls (9.3%, P= 0.024). The association remained after adjustment for age, gender, body mass index, smoking status, history of diabetes, positive family history of CAD, high-density lipoprotein cholesterol, and triglyceride (OR = 1.922; 95% CI [1.146-3.224]; P= 0.013). There was no significant difference in the frequency of any genotype of rs1051931 between the two groups. However, the frequency of the allele V379 was significantly greater in CAD patients with a history of myocardial infarction (MI) than in those without a history of MI (18.7% and 14.8%, P= 0.038). We conclude that there is significant association between the rs16874954 mutation and CAD in the Chinese Han population. The expression of rs1051931 variant in CAD patients may entail increased risk of MI.     

AMI患者治疗前后血浆Hcy和ET检测的临床意义

目的：探讨了急性心肌梗死（AMI）患者治疗前后血浆Hey和ET水平的变化。方法：应用放免法测定了33例AMI患者的血浆Hey和ET含量,并与30名正常健康人作比较。结果：AMI患者在治疗前后血浆Hey和ET水平非常显著地高于正常人组（P〈0．01）,并且呈显著的正相关（r=0．5988,P〈0．01）。经一个月治疗后血浆Hey水平与正常人比较无显著性差异（P〉0．05）,而血浆ET水平与正常人比较仍有显著性差异（P〈0．05）。结论：检测AMI患者血浆Hey和ET水平的变化对临床观察预后有重要的临床价值。     

Genetic Polymorphisms in the CD40 Ligand Gene and Kawasaki Disease

BACKGROUND: Although some previous studies have reported that genetic and immunological factors play important roles in the pathogenesis of Kawasaki disease (KD), the etiological factors of this enigmatical pediatric disease are still poorly understood. PURPOSE: This study aims to investigate whether polymorphisms of the CD40 ligand (CD40L) gene are associated with KD and the development of coronary artery lesions (CAL) in the Taiwanese children. MATERIALS AND METHODS: The CD40L -3459 A/G and IVS4+121 A/G single nucleotide polymorphisms (SNPs) were genotyped in 167 children with KD and 1,010 ethnically matched healthy controls by TaqMan assay. RESULTS: None of the CD40L polymorphisms was associated with susceptibility or CAL development of KD, and this finding was supported by the haplotype analysis. CONCLUSION: In summary, these results provide little support for specific CD40L SNPs in the susceptibility or CAL development of KD in Taiwanese children. However, it will be necessary to validate or replicate this association in other independent large-size ethnic groups.     

AMI患者治疗前后血NO/NOS和ET检测的临床意义

目的:探讨了急性心肌梗死(AMI)患者治疗前后血NO/NOS和ET含量的变化。方法:应用酶法和放免法检测了30例AMI患者血NO/NOS和ET的含量,并与35名正常健康人作比较。结果:AMI患者治疗前血NO水平显著地低于正常人组(P<0.01),而NOS和ET又非常显著地高于正常人组(P<0.01),经治疗后一个月血NO、NOS与正常人比较无显著性差异(P>0.05),而ET与正常人比较仍有显著性差异(P<0.05)。结论:检测AMI患者血NO/NOS和ET水平对临床观察预后有重要的价值。     

NSTEMI患者血清hs-CRP、 cTnI和D-D检测的临床评价

目的:探讨非ST抬高型急性心肌梗死(NSTEMI)患者血清hs-CRP、cTnI和D-D水平变化的临床意义.方法:应用免疫比浊法、生化法和酶联法对66例疑NSTEMI患者进行了血清hs-CRP、cTnI和D-D检测,并根据临床诊断分成观察组和对照组,进行统计学分析.结果:NSTEMI患者血清hs-CRP、cTnI和D-...     

Polymorphisms in the apolipoprotein A5 (APOA5) gene and type III hyperlipidemia

The great majority of patients with type III hyperlipidemia (type III HLP) are homozygous for the epsilon2 allele of the APOE gene. However, only about 10% of epsilon2 homozygotes develop type III HLP, and it has been proposed that additional genetic factors are required for the development of the condition. The frequency of two polymorphisms in the APOA5 gene, -1131T>C and S19W, has been determined in 72 hyperlipidemic patients with APOE2/2 genotype attending a lipid clinic. The frequency of both polymorphisms was significantly higher in APOE2/2 patients than in the normal population. Fifty-three percent of APOE2/2 patients were carriers of one of the polymorphisms compared to 19.7% of controls. Thus, genetic variation in the APOA5 gene is an important cofactor in the development of type III HLP.     

Association between four SNPs on chromosome 9p21 and myocardial infarction is replicated in an Italian population

Genome-wide single nucleotide polymorphism (SNP) association studies recently identified four SNPs (rs10757274, rs2383206, rs2383207, and rs10757278) on chromosome 9p21 that were associated with coronary artery disease (CAD) and myocardial infarction (MI) in Caucasian populations from northern Europe and North America. Our aim was to determine whether these SNPs were associated with MI in a southern Europe/Mediterranean population. We employed a case–control association design involving 416 MI patients and 308 non-MI controls from Italy. Significant allelic association was identified between all four SNPs and MI. The association remained significant after adjusting for covariates for MI (P = 0.007–0.029). One risk haplotype (GGGG; P = 0.028) and one protective haplotype (AAAA; P = 0.047) were identified. Genotypic association analysis demonstrated that the SNPs conferred susceptibility to MI most likely in a dominant model (P = 0.0007–0.013). When the case cohort was divided into a group of MI patients with a family history (n = 248) and one group without it (n = 168), the positive, significant association was identified only in the group with the family history. These results indicate that chromosome 9p21 confers risk for development of MI in an Italian population. G.-Q. Shen, S. Rao, N. Martinelli, L. Li contributed equally to this work.     

Hydroxymethylbilane Synthase Gene Mutations and Polymorphisms in Brazilian Families with Acute Intermittent Porphyria

Acute intermittent porphyria (AIP), an autosomal dominant disorder, is caused by a deficiency of hydroxymethylbilane synthase (HMBS). In the present study, we sought to establish a correlation between HMBS activity with the presence of mutations and polymorphisms. Enzyme activity was measured in red blood cells of four Brazilian unrelated AIP families (n = 124) and in blood donors (n = 80). The HMBS mutations in AIP family members were studied by PCR‐SSCP followed by direct sequencing. Six intragenic SNPs (1345 G>A, 1500 T>C, 2377 C>A, 2478 A>G, 3581 A>G, and 7064 C>A) were determined by PCR‐RFLP. Abnormal SSCP patterns in exons 7, 9, 12, and 15 were observed. DNA sequencing analysis revealed one nonsense mutation, R149X, two missense mutations, G111R and L338P, and one deletion, CT 730–731. All mutation carriers had lower enzyme activity. All polymorphisms, except 2377 C>A and 7064 C>A, showed no significant differences compared with previous reports. Mutation screening allowed the detection of the missense mutation, L338P, and the 730_731delCT deletion, two as yet unreported mutations in Brazilian AIP patients. Our findings also showed a high frequency of 2478 A>G and 3581 A>G polymorphism combinations suggesting that these polymorphisms contributed to enzymatic activity reduction in our study population.     

心脏彩超结合血清cTnI、Mb和FABP检测在AMI中的临床意义

目的:探讨心脏彩超结合血清肌钙蛋白I(cTnI)、肌红蛋白(Mb)和脂肪酸结合蛋白(FABP)测定在急性心肌梗死(AMI)中的临床意义.方法:应用放射免疫分析和酶联法对33例AMI患者进行了血清cTnI、Mb和FABP的测定,并与35名正常健康人作比较.结果:AMI患者血清cTnI、Mb和FABP水平非常显著地高于正常...     

Coronary artery disease with normal lipids and low coronary artery calcium in two women with high lipoprotein(a)

We present 2 patients with elevated levels of lipoprotein (a) and significant coronary artery disease despite having little coronary artery calcification. Clinicians should be aware that patients with elevated lipoprotein (a) may have important coronary artery disease with low coronary artery calcification scores.