OBJECTIVETo investigate the association between the plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene polymorphism and the occurrence of myocardial and cerebrovascular infarctions in individuals from Tianjin, China.

METHODSThe PAI-1 genotype was determined using allele-specific polymerase chain reaction (AS-PCR) in 56 myocardial infarction (MI) patients, 54 cerebrovascular infarction (CI) patients and 83 unrelated healthy controls. All subjects' clinical features and plasma PAI-1 activity levels were determined.

RESULTSThe PAI-1 genotype distribution frequency of the single guanine deletion/insertion 4G/5G polymorphism (located -675 bp upstream from the start of transcription) significantly differed between the patients and healthy controls. In the MI group, the 4G/4G-genotype frequency was increased, but the 4G/5G-genotype is decreased when compared to the control group. In the CI group, both the 4G/4G- and 4G/5G -genotypes occurred at a lower frequency than those in the control group (P < 0.001). The plasma PAI-1 activity level in the MI group was lowered as the presence of the 4G allele decreases. In the CI group, the frequency of 5G/5G was much higher than that of the control group (P < 0.001). The plasma PAI-1 activity level in the CI group was elevated as the presence of the 5G allele increased. Furthermore, positive correlation between triglyceride, glucose levels and PAI-1 activity were found in all three groups (P < 0.001).

CONCLUSIONSThe PAI-1 4G/5G gene polymorphism is associated with a higher risk of MI and CI in individuals in Tianjin, China. The deletion/insertion polymorphism is probably an important hereditary risk factor for heart diseases. Moreover, triglyceride and glucose levels of plasma have functional importance in regulating PAI-1 activity.

Aged ; Asian Continental Ancestry Group ; genetics ; Cerebral Infarction ; genetics ; China ; epidemiology ; Female ; Gene Deletion ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; genetics ; Plasminogen Activator Inhibitor 1 ; genetics ; Polymorphism, Genetic

INTRODUCTIONRecently, there has been increasing evidence that genetic variation in the angiotensin-converting enzyme (ACE) plays an important role in myocardial infarction. Therefore, the present study was carried out with the aim of investigating the association of the ACE gene insertion/deletion (I /D) polymorphism and its levels in myocardial infarction patients and their first-degree relatives (FDRs).

METHODS206 patients with myocardial infarction, 168 FDRs and 210 control subjects were enrolled in the study. ACE I /D polymorphism was determined using the polymerase chain reaction method. Serum ACE levels were measured using the photometric method.

RESULTSThe DD genotype and ACE activity were significantly higher in patients (p-value is 0.00006 and 0.0001, respectively) and FDRs (p-value is 0.003 and 0.04, respectively) compared with the controls.

CONCLUSIONACE DD genotype and ACE levels are important risk factors for myocardial infarction. This study indicates that the higher frequency of the DD genotype and ACE levels observed in FDRs may increase susceptibility to developing myocardial infarction.

Alleles ; Case-Control Studies ; Chi-Square Distribution ; Confidence Intervals ; Ethnic Groups ; genetics ; Female ; Genetic Predisposition to Disease ; epidemiology ; Genetic Variation ; Genotype ; Humans ; Incidence ; India ; epidemiology ; Male ; Myocardial Infarction ; epidemiology ; genetics ; physiopathology ; Odds Ratio ; Peptidyl-Dipeptidase A ; analysis ; genetics ; Polymorphism, Genetic ; Reference Values

OBJECTIVES: The aging process affects responsiveness and other functions of endothelium and vascular smooth muscle cells, predisposing the old vessels to the development of atherosclerotic lesions. Endothelial nitric oxide synthase (ecNOS) gene polymorphisms were shown to affect the occurrence of acute myocardial infarction (AMI). We hypothesized that aging may affect the association between the ecNOS gene polymorphism and AMI. METHODS: We investigated the age-related distribution of the ecNOS gene a/b polymorphism in 121 male AMI patients and 206 age-matched healthy male controls. RESULTS: The aa, ab and bb genotypes were found in 1, 49 and 156 cases among the control subjects and 5, 23 and 93 cases among the AMI patients, respectively. There was a significant correlation between the ecNOS polymorphism and AMI (p +AD0- 0.045). When the correlation was analyzed by age, the significance remained only in the group below the age of 51 (p +AD0- 0.009). The proportion of smokers was increased in the young patients when compared to the old patients (p +AD0- 0.033), indicating that smoking also has greater effect on the younger population. The incidences of hypertension and diabetes mellitus, however, were similar in both populations. CONCLUSION: Our work provides the first evidence that links ecNOS polymorphism to the risk of AMI in relation to age. Young persons who smoke or have ecNOSaa genotype may have an increased risk of developing AMI. The functional as well as structural changes associated with aging in the vascular endothelium may mask the effect of the ecNOS polymorphism in the development of AMI in old persons.
Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Aging/physiology+ACo- ; Chi-Square Distribution ; Comorbidity ; Diabetes Mellitus/epidemiology ; Endothelium, Vascular/enzymology+ACo- ; Genotype ; Human ; Hypertension/epidemiology ; Korea/epidemiology ; Male ; Middle Age ; Myocardial Infarction/physiopathology+ACo- ; Myocardial Infarction/epidemiology ; Nitric-Oxide Synthase/metabolism+ACo- ; Nitric-Oxide Synthase/genetics+ACo- ; Polymerase Chain Reaction ; Polymorphism (Genetics)+ACo- ; Risk Assessment ; Statistics, Nonparametric

OBJECTIVETo investigate the association between the polymorphism of thromboxane synthase gene (CYP5A1) and myocardial infarction (MI) of Uigur nationality patients in Xinjiang.

METHODSRs10487667 site polymorphism in CYP5A1 gene of 318 patients with MI (MI group) and 232 healthy control subjects (control group) were analyzed by polymerase chain reaction and restriction fragment length polymorphism. The serum thromboxane B(2)(TXB(2)) concentration was also detected in all subjects. The relationship of multiple factors and myocardial infarction was evaluated comprehensively by non-condition logistic regression analysis.

RESULTSThe frequencies of CYP5A1 gene Rs10487667 site polymorphism in MI group and control group were: GG type 0.204 (65/318) and 0.155 (36/232), GT type 0.553 (176/318) and 0.466 (106/232), TT type 0.242 (77/318) and 0.379 (88/232), respectively. There was significant difference in frequencies of GG genotype (χ(2) = 12.193, P = 0.002) between two groups and G allele frequency in MI group (0.481 (306/636)) was significant higher than control group (0.388 (180/464)) (χ(2) = 9.449, P = 0.021), but no difference in frequencies of GT and TT genotypes (χ(2) = 0.699, P > 0.05)between controls and MI cases. There was significant difference in serum TXB(2) level between MI ((184.3 ± 34.7) pg/ml) and control ((124.3 ± 28.1) pg/ml) groups (t = 5.503, P = 0.034). In the case and control group, the serum TXB(2) level of the person with GT + GG genotype ((164.21 ± 22.56) and (134.26 ± 19.83) pg/ml)) was significant higher than those of TT genotypes ((113.67 ± 54.23) and (98.54 ± 13.11) pg/ml) (t values were 5.433 and 5.108, respectively, both P values < 0.05). Logistic regression analysis showed that the T allele of the CYP5A1 gene was one independent risk factor of MI (OR = 1.673, 95%CI: 1.020 - 2.156) after adjustment of risk factors.

CONCLUSIONRs10487667 polymorphism in CYP5A1 gene might be a risk factor of MI in Uigur population in Xinjiang, which maybe related with the significant high serum TXB(2) level.

Alleles ; Case-Control Studies ; China ; epidemiology ; Ethnic Groups ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; epidemiology ; genetics ; Polymorphism, Genetic ; Thromboxane B2 ; blood ; Thromboxane-A Synthase ; genetics

Platelet membrane receptor glycoproteins (GP) are essential for the platelet activation process, and the genetic polymorphisms in the genes that encode platelet glycoproteins have been proposed to influence the risk of acute coronary syndrome and atherosclerosis. In this study, we investigated the role of GPIa, HPA-1 and HPA-3 polymorphisms as putative risk factors for myocardial infarction (MI) and the extent of coronary artery disease. We selected 1, 073 subjects who underwent coronary angiography; 242 had normal or minimal coronary atherosclerosis, and 831 patients had significant coronary artery disease (CAD). The genotype was determined by the methods of single base extension for C807T/G873A polymorphisms of GPIa, and restriction fragment length polymorphism for HPA-1 and HPA-3. The C807T and G873A polymorphisms of GPIa showed complete linkage in the Korean population. For HPA-1 gene polymorphism, only the HPA-1a/a (PlA1/A1) genotype was observed in 192 selected subjects from our study population. The distribution of GPIa (C807T/G873A) and HPA-3 genotypes did not differ significantly between normal subjects and CAD subjects. No significant association between MI and both gene polymorphisms was present. However, for the subgroup analysis of young male patients whose age was less than 56 years, the genotype frequency of HPA-3b/b was significantly lower in patients with MI compared to patients without a history of MI (7.5% vs. 20.0%, p=0.04). The odds ratio for HPA-3 b homozygosity versus the HPA-3a carrier was 0.32 (95% CI, 0.10- 0.99, p=0.04). Conclusively, HPA-3 polymorphism was associated with MI in Korean individuals younger than 56 years of age, but other polymorphisms of GP, which we studied, were not associated with both the extent of coronary atherosclerosis or MI.
Aged ; Coronary Arteriosclerosis/epidemiology/*genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease/epidemiology ; Genotype ; Human ; Integrin alpha2/*genetics ; Integrin beta3/*genetics ; Korea ; Male ; Middle Aged ; Myocardial Infarction/epidemiology/*genetics ; Platelet Membrane Glycoprotein IIb/*genetics ; *Polymorphism (Genetics) ; Risk Factors ; Support, Non-U.S. Gov't

OBJECTIVETo assess the association of variations in chemokines (CCL5, CCL2), chemokine receptor (CCR5 and CCR2) genes with susceptibility to myocardial infarction (MI) through a case-control study.

METHODSGenotypes of patients with MI (n = 634) were compared with those of controls (n = 601). Genetic polymorphisms of CCL5 rs2107538 (-403G > A), CCL2 rs1024611 (-2518A > G), CCR5 rs333 ( δ 32 ins or del) and CCR2 rs1799864 (190G > A) of 1235 individuals were determined with polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Particular genotypes were confirmed with DNA sequencing.

RESULTSNo subject was found to carry the CCR5 - δ 32 allele. No association was found between CCL2 rs1024611 and CCR2 rs1799864 polymorphisms and MI. For CCL5 rs2107538 polymorphism, the A allele has occurred at a higher frequency in MI patients than controls, and its AA genotype has been associated with a significantly increased risk of MI independent of conventional risk factors (OR = 3.346, 95%CI = 1.938-5.775, P < 0.01, AA vs. GG). Further analysis indicated that MI patients had significantly more A-403 - A-2518 haplotype (CCL5 -403G > A and CCL2 -2518A > G, 21.8% vs. 26.6%, OR = 1.229, 95%CI = 1.012-1.493, P = 0.038) and AA or AA genotype (CCL5 -403G > A - CCL2 -2518A > G, 5.0% vs. 12.1%, OR = 3.245, 95%CI = 1.780-5.914, P < 0.01).

CONCLUSIONAlthough our data dose not support an association between CCL2 rs1024611, CCR2 rs1799864 and CCR5 rs333 polymorphisms and MI, genetic variation in CCL5 gene may still be a useful marker for assessing susceptibility to MI in ethnic Han Chinese population.

Aged ; Alleles ; Asian Continental Ancestry Group ; ethnology ; genetics ; Base Sequence ; Case-Control Studies ; Chemokine CCL2 ; chemistry ; Chemokine CCL5 ; genetics ; China ; epidemiology ; ethnology ; Female ; Genetic Association Studies ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Myocardial Infarction ; epidemiology ; ethnology ; genetics ; Polymorphism, Single Nucleotide ; Receptors, CCR2 ; genetics ; Receptors, CCR5 ; genetics ; Risk Factors

BACKGROUND/AIMS: Family history (FHx) of coronary heart disease (CHD) is a well-known risk factor for CHD. However, the prognostic implication of FHx has not been established clearly in patients with acute myocardial infarction (AMI). METHODS: In total, 11,612 patients (8,132 males [70%], age 63 +/- 13 years) with first-onset AMI between November 2005 and June 2008 in a nationwide, prospective, multicenter, online registry (the Korea AMI Registry) were analyzed. Clinical characteristics and outcomes (cardiac death and major adverse cardiac events [MACEs]) were assessed according to the presence of FHx. RESULTS: The patients with FHx were younger and included more males. Male patients with FHx included more current smokers and individuals with poor lipid profiles. In all patients, after adjustment using the Cox proportional hazard model, FHx was related to the risk of MACEs (hazard ratio [HR], 1.41; p = 0.009) and cardiac death (HR, 1.56; p = 0.080). The poor prognostic implication of FHx was further augmented in females and a low risk subset of patients. A significant interaction was only found between male and female patients for composite MACEs (p for interaction = 0.057), and between patients with more risk factors (> or = 2 risk factors) and fewer risk factors for cardiac deaths (p for interaction = 0.008). CONCLUSIONS: FHx may be an independent prognostic predictor, especially in female patients and patients with low-risk profile.
Adult ; Aged ; Chi-Square Distribution ; Coronary Artery Bypass ; Coronary Disease/*genetics/mortality/therapy ; Female ; Genetic Predisposition to Disease ; Heredity ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Myocardial Infarction/*genetics/mortality/therapy ; Pedigree ; Percutaneous Coronary Intervention ; Prognosis ; Proportional Hazards Models ; Registries ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Sex Factors ; Time Factors