OBJECTIVETo observe the association between wnt signal pathway and post infarction left ventricular remodeling/rupture in mice with various ages.

METHODSThree months-old (young group, n = 116) and 18 months-old (aged group, n = 116) male C57/BL mice were studied. Seventy mice underwent ligation of left coronary artery, 10 sham-operation and echocardiography and hemodynamics were performed 7 d post-infarction, 36 infarcted mice were used for detecting expression of dvl-1, beta-catenin and connexin 43 in left ventricular (LV) myocardium and infarction region at 3 d, 7 d, 14 d post infarction (n = 12 each).

RESULTSIncidence of cardiac rupture was significantly higher in aged mice than in young mice (36.7% vs. 16.7%, P < 0.05) and degree of LV dilation and contractile dysfunction was significantly severer in aged mice than those in young mice post infarction. Expression of dvl-1, beta-catenin in left ventricle was upregulated in MI group compared with sham group (P < 0.05), expression of dvl-1 and beta-catenin in infarction region in MI 3d group in aged mice was significantly downregulated than in young mice (P < 0.05). Expression of connexin 43 is 2.15 fold higher in young sham mice than in aged sham mice (P < 0.05) and decreased significantly post infarction (P < 0.05). Expression of connexin 43 in infarction region in mice 3 d and 14 d post infarction was significantly lower in aged mice than in respective young mice (all P < 0.05).

CONCLUSIONReductant activation of wnt signal pathway post infarction in aged mice might be responsible for increased incidence of cardiac rupture and aggravated remodeling.

Aging ; Animals ; Heart Rupture ; etiology ; Heart Ventricles ; Male ; Mice ; Mice, Inbred C57BL ; Myocardial Infarction ; metabolism ; pathology ; Myocardium ; metabolism ; Signal Transduction ; Ventricular Remodeling ; Wnt Proteins ; metabolism

OBJECTIVETo investigate the association between the polymorphism of potassium voltage-gated channel, Isk-related family, member 1 (KCNE1) gene and atrial fibrillation (AF) in Uigur patients of Xinjiang.

METHODSThree hundred and three patients with atrial fibrillation and 328 healthy controls were tested for the genotype for the KCNE1 gene SNP in the rs1805127 locus by polymerase chain reaction-restriction fragment length polymorphism. The risk factors were also included.

RESULTSThe genotype frequencies of AA, AG and GG were 0.092 (28/303), 0.386 (117/303) and 0.522 (158/303) in the AF patients while they were 0.122(40/328), 0.485 (159/328) and 0.393 (129/328) in controls. There was significant difference in frequencies of the three genotypes (chi-square was 10.465, P=0.005) and G allele (0.715 vs. 0.636, chi-square was 8.907, P=0.003) between the AF and control groups. Logistic regression analysis showed that the KCNE1 polymorphism was the main risk factor of AF in Uigur population. The OR value of genotype GG was 1.55, the 95% CI: 0.73-3.27.

CONCLUSIONFor Uigur population, genetic polymorphism of rs1805127 locus of the KCNE1 gene may increase the risk of atrial fibrillation.

Asian Continental Ancestry Group ; ethnology ; genetics ; Atrial Fibrillation ; genetics ; Case-Control Studies ; Ethnic Groups ; ethnology ; Exons ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; Potassium Channels, Voltage-Gated ; genetics

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) plays a pivotal role in early atherosclerosis, vascular remodeling and development of atherosclerotic lesion. The potentially functional MMP-9 gene polymorphism may contribute to the susceptibility of acute coronary syndrome (ACS). This study aimed to investigate the association between two single nucleotide polymorphisms (-1562C>T, R279Q) of the MMP-9 gene in patients with ACS in the Uygur population of China. METHODS: This case-control study was composed of 361 ACS patients and 432 control subjects, who had undergone coronary angiography. Among the ACS patients, 162 (44.9％) had single-vessel disease, 145 (40.2％) had two-vessel disease, and 54 (14.9％) had three-vessel disease. The genotypes of the two selected SNPs were determined by the method of polymerase chain reaction and restriction fragment length polymorphism (RFLP-PCR). The relationship between the polymorphism of the MMP-9 gene and the severity of coronary arterial stenosis was analyzed. RESULTS: Analysis of the two SNPs showed that the frequency of CT and TT genotypes in patients with ACS was significantly higher than that in the control group (ACS vs. controls; CT+TT:25.5％ vs. 15.8％, P=0.001). And the -1562 gene allele (C/T) was significantly associated with acute coronary syndrome (ACS vs. controls; C allele: 85.7％ vs. 91.5％, T allele: 14.3％ vs. 8.5％, P<0.001). But the frequencies of CT+TT and CC genotypes were not statistically different among ACS patients with one, two and three or more significantly diseased vessels (P=0.55). The R279Q polymorphism site with regard to the association with ACS was not significant (P>0.05). The presence of CT or TT genotypes, assuming codominant effect of the T allele, was independently associated with increased risk of coronary artery disease when adjustment was made for age, body mass index, smoking, hypertension and diabetes mellitus [odds ratio=1.737 (95％ confidence interval, 1.337-2.257), P=0.018]. CONCLUSIONS: MMP-9-1562C>T polymorphism is associated with the susceptibility to ACS in the Uygur population of China. However, this mutation apparently is not related to the severity of coronary arterial stenosis. Another SNP (R279Q) polymorphism of MMP-9 is not significantly associated with the risk of ACS.

Objective To investigate the prevalence and distributing feature of overweight and obesity in Han, Uygur and Hazakh population in adults from Xinjiang. Methods Four-stage selected random samples with maternal age at 35 or over were used to analyze the prevalence and distributing feature of self-reported congestive heart failure in different nationalities, age, sex. The sampled adult population were collected from 6 localities(Urumqi, Kelamayi, Fukang, the Turfan Basin locality, Hetian locality, Yili Hazakh autonomous prefecture), 23 municipalities and 7 locality and 5 autonomous counties in Xinjiang. Results 16 460 people were surveyed. The prevalence rates of overweight and obesity were 36.1% and 26.9% in Han, Uygur and Hazakh population in Xinjiang,respectively from February, 2007. The prevalence rates of overweight and obesity were 41.4% and18.4% in Han population, 34.9% and 28.9% in Uygur population, but 32.8% and 40.1% in Hazakh population. The prevalence rate of overweight and obesity was higher in males(x2= 135.00, P＜0.05).The prevalence rates of overweight and obesity were different between different ethnic groups(x2=338.232, P＜0.05). The prevalence of overweight was highest in Han population, with the highest seen in Hazakh population. The prevalence rates of overweight and obesity were increasing with age (x2=246.80,P＜0.05). The overweight rate in 45-54 year olds and the obesity rate in 55-64 year olds reached their peak values. Results from logistic regression model analyses indicated that the prevalence of overweight and obesity in Xinjiang were statistically associated with age, educational level, jobs, smoking and alcohol consumption. Conclusion The prevalence rates of overweight and obesity were much higher in the population of Xinjiang but different among ethnicities. The prevalence of overweight was the highest in Han male population and the rate of obesity in Hazakh male population was the highest.

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

Objective The purpose of this study was to investigate the association of genetic polymorphism of cyclooxygenase-2 and prostacyclin synthase with myocardial infarction (MI)in Uigur population in Xinjiang. Methods 178 patients with MI and 175 healthy control subjects were detected on the genetic polymorphism of cyclooxygenase-2 and prostacyclin synthase by polymerase chain reaction-based restriction fragment length polymorphism. Other serum 6-keto-PGF1α concentration and biochemical indicators were detected in all the subjects. Results (1)The genotype distributions of the control group and MI group were in the Hardy-Weinberg equilibrium. The frequencies of CC, CA and AA genotype of prostacyclin synthase were 75.84%, 17.42% and 6.74% in MI group while they were 64.57%, 28.29% and 9.14% in controls respectively. There was significant difference in frequencies of CC genotype and C allele as well as CA and AA genotypes between controls and MI cases. (2)The frequencies of -765GG,-765GC and -765CC genotype of cyclooxygenase-2 were 78.65%, 19.66% and 1.69% in MI group while they were 55.43%, 34.86% and 9.71% in controls respectively. There was significant difference in frequencies of three genotypes and alleles between the two groups (P＜0.05 or P＜0.01 ). (3) In combined genotype analysis, the genotype of PGIS CC + COX-2 -765GG was significantly higher in patients with MI than in control subjects (P＜0.05). The odds ratio estimated through combined analysis of the PGIS CC and COX-2 -765GG genotypes(OR=3.87) markedly increased when compared with that estimated separately from the PGIS CC ( OR=1.72 ) or COX-2 -765GG ( OR = 2.94 ) genotype. (4)There was a significant difference in serum 6-keto-PGF1α level between MI group and control group (P＜0.05 ), but there were no differences found in every genotype of PGIS and COX-2 gene (P＞0.05 ). In the cases with both COX-2 -765GG and PGIS CC genotypes, the serum 6-keto-PGF1α levels was lower than that of others (P＜0.05). Conclusion The CC genotype and C allele of prostacyclin synthase, -765GG genotype and G allele of COX-2 might serve as risk factors of MI of Uigur population in Xinjiang.Populations with both COX-2 -765GG and PGIS CC genotypes were more at risk with MI than others which might be resulted from the decreased serum 6-keto-PGF1α concentration. The -765CC genotype and C allele of COX-2 gene might have protective functions on MI among Uigur population in Xinjiang.

Objective The aim is to investigate the association between coronary heart disease (CHD) and c.553G＞T polymorphism of apolipoprotein A5 (ApoA5) gene and the influence of serum lipid level in the Hah ethnic population of Xinjiang. Methods The polymorphism of ApoA5 gene in 486 patients with CHD and 501 controls was analyzed by methods of polymerase chain reaction and restriction fragment length polymorphism analysis. Level of serum lipid in each patient was detected at the same time. Results There was significant difference in the distribution of genotypes between CHD group and controls group ( x2 = 8.757, P= 0.013 ). Non-conditioned logistic regression analyses, after adjusted for age, gender, smoking, total serum cholesterol, presence of hypertension and diabetes, revealed that individuals who carried T allele (TT + GT genotype) had an increased risk of CHD, compared to GG genotype (OR= 1.753,95%CI: 1.030-2.983, P＜0.05 ). There was also a remarkable difference noticed in the level of serum triglyceride by genotypes in CHD group and control group (t=5.242, P＜0.01; t=-3.499, P=0.001 ). Individuals in the two groups who carried T allele had higher level of serum triglyceride than those carried GG genotype. Individuals in CHD group who carried T allele had higher level of serum total cholesterol than those carried GG genotype (t=-2.465, P=0.014). Conclusion It seemed that the c.553G＞T polymorphism of ApoA5 gene had influenced on the level of serum triglyceride and the total cholesterol among Han population in Xinjiang. c.553G＞T polymorphism was associated with the development of CHD, while T allele might be an influencing risk factor on CHD.

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

METHODSThree hundred and fifteen patients with MI and 218 healthy control subjects were detected by polymerase chain reaction and restriction fragment length polymorphism. The serum thromboxane B2 (TXB2) in all subjects was detected with radioimmunoassay kit.

RESULTSThe genotype distributions of the MI group and control group were in Hardy-Weinberg equilibrium (Chi-square=0.375,0.029, P>0.05). The frequencies of CC and TC were 0.933 and 0.067 in MI group while they were 0.977 and 0.023 in controls. There was significant difference in frequencies of the TC genotype and T allele but no difference in frequencies of CC genotype between controls and MI cases. There was significant difference in serum TXB2 level between the MI and control group (P<0.05), and between individuals of the TC and CC genotypes (P<0.05). The serum TXB2 level in the MI cases with TC genotype was increased compared with that of other genotypes (P<0.05).

CONCLUSIONThe TC genotype and T allele of thromboxane synthase gene might be risk factors of MI in Uigur population in Xinjiang, which might result from the increased serum TXB2 level.

Adult ; Asian Continental Ancestry Group ; ethnology ; genetics ; Base Sequence ; Case-Control Studies ; China ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation, Missense ; Myocardial Infarction ; blood ; enzymology ; ethnology ; genetics ; Polymorphism, Genetic ; Thromboxane B2 ; blood ; Thromboxane-A Synthase ; genetics

OBJECTIVETo investigate the association between the polymorphism of prostacyclin synthase gene (CYP8A1) and myocardial infarction (MI) in Uigur population.

METHODSTotally 210 patients with MI and 206 healthy control subjects were detected by polymerase chain reaction and restriction fragment length polymorphism. The serum 6-keto-PGF(1alpha) was detected with radioimmunoassay kit in all subjects.

RESULTSThe frequencies of CC, AC and AA were 0.024 (5/210), 0.124 (26/210) and 0.852 (179/210) in MI group while ones those 0.010 (2/206), 0.073 (15/206) and 0.917 (189/206) in the controls. There was no significant difference in frequencies of CC, AC and AA genotypes between controls and MI cases (chi(2) = 0.782, P > 0.05), but the frequency of CC + AC genotype in MI group [0.14 (31/210)] was higher than that in the controls [0.083 (17/206)] giving significant difference (chi(2) = 4.321, P = 0.031). The C allele frequency in the MI group [0.086 (36/420)] was higher than that in the controls [0.046 (19/412)] showing significant statistical difference (chi(2) = 5.284, P = 0.021). There was significant difference (t = 6.255, P < 0.01) in serum 6-keto-PGF(1alpha) level between MI group [(17.40 +/- 4.56) pg/ml] and control group [(20.34 +/- 5.02) pg/ml]. In the cases and control group, the serum 6-keto-PGF(1alpha) level of the persons with CC + AC genotype [(14.30 +/- 3.31) pg/ml, (18.31 +/- 4.62) pg/ml] was lower than those of AA genotypes [(19.34 +/- 5.51) pg/ml, (25.10 +/- 5.00) pg/ml], and the statistical significance was also observed (t' = 6.934, P < 0.05; t = 5.393, P < 0.01). Logistic regression analysis showed that the C allele of the CYP8A1 gene was an independent risk factor for MI (OR = 1.77; 95% CI: 1.06 - 2.05).

CONCLUSIONThe C allele of CYP8A1 might be a risk factor of MI in Uigur population, and be resulting from the decrease of serum 6-keto-PGF(1alpha) level for gene variation.

Aged ; Alleles ; Asian Continental Ancestry Group ; genetics ; Cytochrome P-450 Enzyme System ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Intramolecular Oxidoreductases ; genetics ; Male ; Middle Aged ; Myocardial Infarction ; ethnology ; genetics ; Polymorphism, Genetic ; Population Groups

OBJECTIVETo explore the effects of ischemia postconditioning (IPC) on ischemia-reperfusion (I/R) injury and associated reperfusion injury salvage kinase (RISK) signal transduction pathways changes in isolated mouse hearts.

METHODSLangendorff perfused C57/BL mouse hearts were divided to 6 groups: (1) control: 30 min global ischemia and 2 h reperfusion (I/R); (2) IPC with 3 episodes, IPC with 3 episodes of 10 s of ischemia and 10 s reperfusion after 30 min ischemia and before 2 h reperfusion; (3) IPC with 6 episodes, IPC with six episodes of 10 s of ischemia and 10 s reperfusion after 30 min ischemia and before 2 h reperfusion; (4) delayed IPC, IPC with 3 episodes of 10 s of ischemia and 10 s reperfusion after 30 min ischemia and at one minute after reperfusion; (5) IPC + ERK1/2 inhibitor PD98059 (10(-5) mol/L for 15 min); (6) I/R + ERK1/2 inhibitor PD98059 (10(-5) mol/L for 15 min). The effects of IPC on hemodynamics, coronary artery flow, creatine kinase (CK) and lactate dehydrogenase (LDH) release, myocardial SOD, MDA, phospho-protein kinase (P-ERK1/2) and phospho-protein kinase B (P-Akt) as well as myocardial infarction size were measured.

RESULTSIPC with 3 episodes and IPC with 6 episodes significantly and equally improved myocardial function, increased myocardial SOD, reduced CK and LDH release and myocardial infarction size compared with IR group (all P < 0.01) while these parameters were similar between I/R hearts and delayed IPC hearts. IPC significantly increased myocardial ERK1/2 phosphorylation, PD98059 inhibited the phosphorylation of ERK1/2 and abolished the cardioprotective effects induced by IPC.

CONCLUSIONSIPC obviously attenuated I/R injury in isolated mouse hearts, the cardioprotection of IPC was not enhanced because of increasing of IPC episodes and disappeared in delayed IPC. The cardioprotective effects of IPC were mediated through ERK1/2-MAPK signal transduction pathway.

Animals ; Disease Models, Animal ; Ischemic Preconditioning, Myocardial ; Mice ; Mice, Inbred C57BL ; Mitogen-Activated Protein Kinases ; metabolism ; Myocardial Ischemia ; metabolism ; therapy ; Myocardial Reperfusion Injury ; metabolism ; therapy ; Signal Transduction