β3-adrenoceptor (β3-AR) has been shown to promote myocardial apoptosis. However, the exact physiological role and importance of this receptor in the human myocardium, and its underlying mode of action, have not been fully elucidated. The present study aimed to determine the effects of β3-AR on the promotion of myocardial apoptosis and on norepinephrine (NE) injury. We analyzed NE-induced cardiomyocyte (CM) apoptosis by using a TUNEL and an annexin V/propidium iodide apoptosis assay. Furthermore, we investigated the NE-induced expression of the apoptosis marker genes Akt and p38MAPK, their phosphorylated counterparts p-Akt and p-p38MAPK, caspase-3, Bcl-2, and Bax. In addition, we determined the effect of a 48-h treatment with a β3-AR agonist and antagonist on expression of these marker genes. β3-AR overexpression was found to increase CM apoptosis, accompanied by an increased expression of caspase-3, bax/bcl-2, and p-p38MAPK. In contrast, the β3-blocker reduced apoptosis of CMs and the associated elevated Akt expression. We identified a novel and potent anti-apoptosis mechanism via the PI3K/Akt pathway and a pro-apoptosis pathway mediated by p38MAPK.
Adrenergic Agonists ; pharmacology ; Adrenergic Antagonists ; pharmacology ; Animals ; Apoptosis ; Cells, Cultured ; Myocytes, Cardiac ; drug effects ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta-3 ; genetics ; metabolism ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases ; metabolism

Objective To investigate the prevalence rates of diabetes mellitus and its associated risk factors in children with Han,Uygur and Kazak ethnicities in Xinjiang.Methods A cross-sectional random samples involving aged 0-17 years were carried out to analyze the prevalence rates and associated risk factors of diabetes mellitus in children of Han,Uigur and Kazak ethnicities from 3 prefectures (Hetian,Kashi and Fuhai) in Xinjiang Autonomous Regions.Diabetes mellitus and impaired fasting glucose (IFG) were defined by the China Diabetes Prevention and Control Standard set in 2007.Data was collected through filling in the questionnaires and results from physical examination and laboratory tests.Results The total prevalence rates of IFG and diabetes mellitus were 0.68％ and 0.09％,respectively.Data from logistic regression analysis suggested that overweight and obesity were risk factors for diabetes mellitus in children from Xinjiang,with odds ratio values as 2.844 and 3.963,respectively.Conclusion Children with Han,Uygur and Kazak ethnicities in Xinjiang had an overall standardized prevalence rates of diabetes mellitus.IFG were 0.57％ and 1.35％lower than the 2004 data from children at same age groups in Beijing and the whole nation,also 0.19％lower then the national rate of 5-17 years-old children juvenile diabetes.

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

OBJECTIVETo investigate the association between matrix metalloproteinase 9 gene (MMP9) -1562C/T polymorphism and myocardial infarction (MI) in Uighur population of Xinjiang.

METHODSA total of 347 patients with MI evidenced by coronary arteriography, and 403 controls free from coronary artery disease with normal angiograms were recruited for the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the -1562C/T functional promoter polymorphism of the MMP9 gene. The relationship between the polymorphism and the severity of coronary arterial stenosis was analyzed.

RESULTSThe results showed that the frequency of CT and TT genotypes in patients with MI (27.67%) was significantly higher than that in controls (14.14%). The frequencies of the -1562T allele were 15.71% and 7.56% in the MI group and the control group respectively (chi-square=24.57, P<0.01). Logistic regression analysis indicated that the T allele carriers (CT+TT) had significantly increased risk of MI compared with the CC carriers (OR=2.009, 95%CI: 1.250-3.230). Individuals carrying the -1562T allele with diabetes mellitus were at an increased risk of MI (OR=3.714, 95%CI: 1.299-10.773). The frequencies of CT and TT genotypes were not significantly different among MI patients with one, two and three or more significantly diseased vessels (chi-square=0.491, P=0.782).

CONCLUSIONThe -1562C/T polymorphism in the MMP9 gene promoter is associated with the susceptibility to MI in the Uighur population of Xinjiang. The T allele might be a risk factor of MI. And there was a coordinated effect between the -1562T allele and diabetes mellitus in the development of MI. The -1562C/T polymorphism may not be a predictor of the severity of coronary atherosclerosis.

China ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Matrix Metalloproteinase 9 ; genetics ; Middle Aged ; Myocardial Infarction ; enzymology ; genetics ; Polymorphism, Single Nucleotide

OBJECTIVETo explore the association between genetic polymorphism of serum amyloid protein A1 (SAA1) with carotid intima media thickness in a healthy Han Chinese population of Xinjiang.

METHODSA total of 449 healthy Han Chinese participating the cardiovascular risk survey between June 2007 and September 2009 were included, the genotypes of the SAA1 were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The mean IMT of the right and left common carotid arteries were measured by B-mode ultrasonography.

RESULTS(1) There was strong linkage disequilibrium between rs12218 and rs2229338 (D' = 0.89). (2) The carotid common IMT (CC-IMT) and the carotid bulb IMT (CB-IMT) were similar between the AA genotype (wild genotype) and the GGFAG genotype (mutational genotype) in rs2229338 of SAA1 gene. (3) CC-IMT [(0.081 ± 0.071) cm vs (0.068 ± 0.019) cm, P = 0.01] was significantly thicker in CC + CT genotype (mutational genotype) group than in TT genotype (wild genotype) of rs12218 group and the difference remains significant after adjustment for age, gender, blood pressure, waist circumference, creatinine and high density lipoprotein cholesterol. CB-IMT [(0.085 ± 0.038) cm vs. (0.081 ± 0.052) cm, P = 0.36] was similar between CC + CT genotype and TT genotype of rs12218 groups.

CONCLUSIONOur results suggested that the genetic polymorphism of SAA1 might be linked with IMT and rs12218 mutation could serve as a promoting factor for IMT in Han Chinese people.

Aged ; Asian Continental Ancestry Group ; genetics ; Carotid Intima-Media Thickness ; Female ; Humans ; Linkage Disequilibrium ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Serum Amyloid A Protein ; genetics

OBJECTIVETo investigate the association of the -12238T/C polymorphism of apolipoprotein A5 (APOA5) gene with coronary heart disease (CHD) and the influence of serum lipid levels in Chinese Uygur population of Xinjiang.

METHODSThe -12238T/C polymorphism of APOA5 gene in 344 patients with CHD and 408 controls was analyzed by polymerase chain reaction-restriction fragment length polymorphism; the serum lipid levels were detected as well.

RESULTSThe frequencies of CC, TC and TT genotype were 6.69%, 43.31% and 50.00% in the CHD group, while they were 14.95%, 45.10% and 39.95% in the control group. There was significant difference in the distribution of genotypes between the two groups (P < 0.01). Logistic regression analyses adjusted for age, gender, smoking, serum total cholesterol, presence of hypertension and diabetes revealed that individuals carrying CC genotype had an increased risk of CHD compared with TT genotype (OR = 0.328, 95%CI: 0.154-0.700). There was also significant difference in serum triglyceride level in genotypes between these two groups (P < 0.01). Patients in CHD group who carried CC and TC genotypes had lower serum triglyceride level than the TT genotype carriers.

CONCLUSIONThe -12238T/C polymorphism of APOA5 gene has influence on the serum triglyceride level in Uygur population of Xinjianxg. This polymorphism might be associated with development of CHD, and the CC genotype might be a protective factor in the development of CHD.

Adult ; Aged ; Apolipoprotein A-V ; Apolipoproteins A ; genetics ; Asian Continental Ancestry Group ; genetics ; China ; ethnology ; Coronary Disease ; blood ; ethnology ; genetics ; Ethnic Groups ; genetics ; Female ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Polymorphism, Genetic ; Triglycerides ; blood

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 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.

Objective To investigate carotid artery intima-media thickness (IMT) and the correlated risk factors in Han, Uygur, Hazakh residents over 35 years old of Xinjiang Uygur autonomous region. Method Cross-sectional and cluster sampling random selected method was carried out for residents over 35 years old in Han, Uygur, Hazakh population of Xinjiang to investigate IMT and correlated risk factors. Results IMT of Han, Uygur, Hazakh residents over 35 years old of Xinjiang Uygur autonomous region was (0. 0761 ± 0. 0283 ) cm, (0. 0663 ± 0. 0262) cm, and (0. 0781 ± 0. 0274 ) cm, respectively. There were significantly difference between various nationality( all P ＜0. 05 ). IMT was thicker in male Han people than in female Han people [(0. 0807 ± 0. 0288 )cm vs. (0. 0717 ± 0. 0270 ) cm, P ＜ 0. 01] and in male Uygur than in female Uygnr residents [(0. 0706 ±0. 0270)cm vs. (0. 0633 ±0. 0252)cm, P ＜0. 01]and in male Hazakh and female Hazakh residents [(0. 0794 ± 0. 0280) cm vs. (0. 0768 ± 0. 0268 ) cm, P ＜ 0. 01].Linear correlation analysis showed that age ( r = 0. 176, P ＜ 0. 05 ), systolic blood pressure ( r = 0. 168, P ＜ 0. 05 ), diastolic blood pressure ( r = 0. 167, P ＜ 0. 05 ), fasting blood glucose ( r = 0. 053, P ＜ 0. 05 ), total cholesterol(r = 0.097,P ＜ 0.05) and ankle brachial index (r = 0.067, P ＜ 0.05) were significantly correlated with IMT. Conclusions Our results showed that IMT was thicker in Hazakh residents than in Han and Uygnr residents. IMT was closely related to known cardiovascular risk factors including age,systolic blood pressure,diastolic blood pressure,fasting blood glucose, total cholesterol and ankle brachial index level.

Objective The aim of this study was to evaluate the prevalence of abnormal ankle brachial index(ABI) in Xinjiang adult population. Method Random samples maternal age 35 and over were used to analyze the prevalence and distributing feature of self-reported abnormal ABI among different nationality in 7 municipalities and locality and 26 community and autonomous county in Xinjiang. Results A total of 14 618 adults were surveyed. The prevalence of abnormal ABI was 1.26％. The prevalence of abnormal ABI was 3.56％, 7.05％ and 5.79％ in Han, Uygur and Hazakh population, respectively.Incidence of abnormal ABI was significantly higher in females than in males (6. 65％ vs 3. 74％, X2 =58.79,P =0.00). Gender, nationality, systolic blood pressure, body mass index were independent predictors for abnormal ABI. Conclusions The results of this study showed higher prevalence rate of abnormal ABI, especially in females, in Xinjiang. Nationality and gender are predictors for abnormal ABI.