OBJECTIVETo identify the relationship between angiotensin-converting enzyme (ACE) gene polymorphism and heart rate variability in cerebral stroke patients.

METHODSAn insertion/deletion(I/D) polymorphism of the ACE gene was analyzed by polymerase chain reaction in 43 normal subjects, 46 patients with ischemic cerebral stroke, and 40 patients with brain hemorrhage; their heart rate variability(HRV) parameters such as time domain and power spectral component were analyzed.

RESULTSThe frequency of DD genotype and the frequency of deletion alleles in cerebral stroke groups were significantly higher than those in control groups (P<0.01), and the measured components of HRV, including total power (TP), low frequency power (LF), high frequency power (HF), LF/HF, and choas, were higher in the patients with the ACE DD genotype when compared with those in the patients with the ACE II, ID genotypes; there was significant difference in effective rate (P<0.05).

CONCLUSIONThe above related parameters of HRV were correlated with heritability, suggesting that the cerebral stroke patients with the ACE DD genotype are at high risk of cerebrogenic cardiac autonomic nerve function disturbances.

Aged ; Female ; Genotype ; Heart Rate ; Humans ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; Stroke ; genetics ; physiopathology

Oxidative stress may reduce cardiovascular function. Glutathione Stransferases(GSTs) play an important role in cell defending against oxidative stress. Glutathione S-transferase P1 (GSTP1) gene is one of the most intensively investigated glutathione S-transferase genes in epidemiologic studies. The GSTP1 gene displays a polymorphism at codon 105 (Ile105 Val), which results in an enzyme with altered substrate affinity. To date, there have been few studies evaluating whether Ilel05Val polymorphism of GSTP1 gene has an effect on cardiovascular function in the broad masses of people. In this study, we investigated the relationship between Ile105 Val polymorphism of GSTP1 gene and heart rate and blood pressure in 197 unrelated adult males of Han nationality. It was found that there were two types of the GSTP1 genotypes, Ile105/Ile105 and Ile105/Val105, but genotype Val105/Val105 was not found, and the frequencies of IleIes/Ileos and Ile105/Val105 genotypes were 78% and 22% respectively. Comparison with individuals with lie105/Val105 genotype showed that those with Ile105/Ile105 genotype had higher rest heart rate and maximal heart rate mean values. However, whether for rest heart rate and maximal heart rate or for heart rate reserve, no significant differences were found between the two genotype groups (P>0.05). Compared with individuals with Ile105/Val105 genotype, those with Iler105/Ile105 genotype had higher systolic blood pressure and pulse pressure mean values and lower diastolic blood pressure mean value. However, for systolic blood pressure, diastolic blood pressure and pulse pressure, no significant differences were found between the two genotype groups (P>0.05). The results suggested that Ile105 Val polymorphism of GSTP1 gene may not be associated with heart rate and blood pressure in the broad masses of people.
Adult ; Blood Pressure ; physiology ; Genotype ; Glutathione S-Transferase pi ; genetics ; Heart Rate ; physiology ; Humans ; Male ; Polymorphism, Genetic

OBJECTIVE: To assess the association of polymorphisms of receptor of advanced glycation end products (RAGE) gene, monocyte to high-density lipoprotein cholesterol ratio (MHR) and variability of heart rate among patients with coronary heart disease (CHD). METHODS: 120 patients with CHD and 120 healthy individuals were respectively selected as the observation group and the control group. Allelic and genotypic differences of -429T>C, 1704G>T, 82G>S, MHR ratio and heart rate variability between the two groups and patients with different severity were analyzed. The correlation between their genotypes and MHR ratio and heart rate variability was analyzed. RESULTS: The 82G>S polymorphism of the RAGE gene and the allelic difference between the two groups and patients with different severity were statistically significant (P< 0.05). Compared with the control group and patients with mild to moderate phenotype, monocyte, total cholesterol, triglyceride, low density lipoprotein, MHR, low frequency in the observation group and patients with severe symptoms were significantly higher, while their high density lipoprotein, standard deviation of NN intervals (SDNN), standard deviation average of NN intervals (SDANN), root mean square successive differences, percentage of differences exceeding 50ms between adjacent normal number of intervals (PMN50), high frequency (HF) were significantly lower. The gene frequencies of G-Gly-T, T-Gly-T, G-Ser-T and G-Gly-C were correlated with SDNN, SDANN, rMSSD, PMN50, HF and MHR, but negatively correlated with low frequency. CONCLUSION Polymorphisms of the RAGE gene in patients with coronary heart disease are associated with the MHR ratio and heart rate variability, which can be used as markers for the diagnosis and efficacy evaluation.
Antigens, Neoplasm ; Coronary Disease/genetics* ; Gene Frequency ; Glycation End Products, Advanced ; Heart Rate ; Humans ; Mitogen-Activated Protein Kinases ; Polymorphism, Genetic

PURPOSE: Recently, mitochondrial DNA 4977bp deletion (mtDNA4977-mut), a somatic mutation related to oxidative stress, has been shown to be associated with atrial fibrillation (AF). We hypothesized that patient age, as well as electroanatomical characteristics of fibrillating left atrial (LA), vary depending on the presence of mtDNA4977-mut in peripheral blood among patients with non-valvular AF. MATERIALS AND METHODS: Analyzing clinical and electroanatomical characteristics, we investigated the presence of the mtDNA4977-mut in peripheral blood of 212 patients (51.1+/-13.2 years old, 83.5% male) undergoing catheter ablation for non-valvular AF, as well as 212 age-matched control subjects. RESULTS: The overall frequency of peripheral blood mtDNA4977-mut in patients with AF and controls was not significantly different (24.5% vs. 19.3%, p=0.197). When the AF patient group was stratified according to age, mtDNA4977-mut was more common (47.4% vs. 20.0%, p=0.019) in AF patients older than 65 years than their age-matched controls. Among AF patients, those with mtDNA4977-mut were older (58.1+/-11.9 years old vs. 48.8+/-11.9 years old, p<0.001). AF patients positive for the mtDNA mutation had greater LA dimension (p=0.014), higher mitral inflow peak velocity (E)/diastolic mitral annular velocity (Em) ratio (p<0.001), as well as lower endocardial voltage (p=0.035), and slower conduction velocity (p=0.048) in the posterior LA than those without the mutation. In multivariate analysis, E/Em ratio was found to be significantly associated with the presence of mtDNA4977-mut in peripheral blood. CONCLUSION: mtDNA4977-mut, an age-related somatic mutation detected in the peripheral blood, is associated with advanced age and electro-anatomical remodeling of the atrium in non-valvular AF.
Adult ; Aged ; Atrial Fibrillation/blood/*genetics/*physiopathology ; Atrial Remodeling/*genetics ; Base Pairing/*genetics ; Case-Control Studies ; DNA, Mitochondrial/*blood/*genetics ; Female ; Heart Atria/pathology/physiopathology ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; Male ; Middle Aged ; Mutation Rate ; Phenotype ; Sequence Deletion/*genetics

Elevated heart rate has been proposed as an independent risk factor for cardiovascular diseases, but their interrelationships are not well understood. In this study, we performed a genome-wide linkage scan in 1,026 individuals (mean age 30.6 years, 54.5% women) from 73 extended families of Mongolia and determined quantitative trait loci that influence heart rate. The DNA samples were genotyped using deCODE 1,039 microsatellite markers for 3 cM density genome-wide linkage scan. Correlation analysis was carried out to evaluate the correlation of the covariates and the heart rate. T-tests of the heart rate were also performed on sex, smoking and alcohol intake. Consequently, this model was used in a nonparametric genome-wide linkage analysis using variance component model to create a multipoint logarithm of odds (LOD) score and a corresponding P value. In the adjusted model, the heritability of heart rate was estimated as 0.32 (P<.0001) and a maximum multipoint LOD score of 2.03 was observed in 77 cM region at chromosome 18. The second largest LOD score of 1.52 was seen on chromosome 5 at 216 cM. Genes located on the specified locations in chromosomes 5 and 18 may be involved in the regulation of heart rate.
Adolescent ; Adult ; Chromosome Mapping/*methods ; Female ; Genetics, Population ; Genome, Human/*genetics ; Genome-Wide Association Study/methods ; *Heart Rate ; Humans ; Linkage (Genetics) ; Male ; Middle Aged ; Mongolia ; Quantitative Trait Loci/*genetics ; Young Adult

BACKGROUNDGenetic factors can influence antihypertensive response to metoprolol, and many studies focused on the relationship between the genotype in beta1-adrenergic receptor and blood pressure (BP), little was known about the association of angiotensin-converting enzyme (ACE) genotype with the therapeutic result of metoprolol. The present study aimed to investigate whether the ACE gene insertion (I)/deletion (D) polymorphism is related to the response to metoprolol in Chinese Han hypertensive patients.

METHODSNinety-six patients with essential hypertension received metoprolol (100 mg once daily) as monotherapy for 8 weeks. Twenty-four hours ambulatory blood pressure monitoring and dynamic electrocardiogram were performed before and after treatment. Genotyping analysis was performed using PCR. The association of the ACE gene I/D polymorphism with variations in BP and heart rate (HR) was observed after the 8-week treatment.

RESULTSThe patients with ACE gene II polymorphism showed greater reduction in 24-hour average HR than those with ID or DD polymorphisms (P = 0.045), no effect of this genotype on the reduction in seating HR or in BP was observed. After adjusting for age, gender, body mass index, BP and HR at baseline, the ACE gene I/D polymorphism was still an independent predictor for variations in 24-hour average HR.

CONCLUSIONSThe II polymorphism in ACE gene could be a candidate predictor for greater reduction in 24-hour average HR in Chinese Han hypertensive patients treated by metoprolol. Greater benefits would be obtained by patients with II polymorphism from the treatment with metoprolol. Larger studies are warranted to validate this finding.

Adult ; Aged ; Antihypertensive Agents ; therapeutic use ; Female ; Genotype ; Heart Rate ; drug effects ; genetics ; Humans ; Hypertension ; drug therapy ; genetics ; Male ; Metoprolol ; therapeutic use ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; genetics

OBJECTIVETo study the relationship between resting heart rate and single nucleotide polymorphisms (SNP) at 3 sites of nitric oxide synthase (NOS) gene including NOS3 -922A/G, NOS3 894G/T and NOS2 -1173C/T SNPs.

METHODSGenomic DNA was gained from 211 Chinese Han nationality population. The SNPs of NOS3 -922A/G, NOS3 894G/T and NOS2 -1173C/T were genotyped by allele-specific primer-polymerase chain reaction (ASP-PCR) technique.

RESULTSThe distribution frequencies of GG, GT and TT genotypes of NOS3 894G/T and AA, AG and GG genotypes of NOS3 -922A/G and CC, CT and TT genotypes of NOS2 -1173C/T were consistent with Hardy-Weinberg equilibrium (P> 0.05). The resting heart rate of Chinese Han nationality population with AA genotypes was higher than that with GG genotype of NOS3 -922A/G (P< 0.01). The resting heart rate of the sub-population with GG genotype was higher than that with TT genotype of NOS3 894G/T (P< 0.05). There were no difference among the resting heart rates of the sub-populations with the allele genotypes of NOS2 -1173C/T.

CONCLUSIONThe resting heart rate of Chinese Han nationality population with mutated genotype GG of NOS3 -922A/G and with mutated genotype TT of NOS3 894G/T were lower than those with wild genotype of NOS3 -922A/G and NOS3 894G/T. The finding suggests that resting heart rate is associated with SNP of NOS3 -922A/G and NOS3 894G/T.

Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Gene Frequency ; Genotype ; Heart Rate ; Humans ; Male ; Middle Aged ; Nitric Oxide Synthase ; genetics ; Nitric Oxide Synthase Type II ; genetics ; Nitric Oxide Synthase Type III ; genetics ; Polymorphism, Single Nucleotide

OBJECTIVETo assess the effects of penehyclidine hydrochloride on patients with acute lung injury (ALI), to observe the expression of Toll-like receptor 4 (TLR4) on the peripheral monocytes of ALI patients and changes of inflammatory and anti-inflammatory cytokines and to investigate the mechanism of TLR4 in ALI.

METHODSForty-five patients with ALI were randomly divided into penehyclidine hydrochloride treatment group (P group, n equal to 21) and conventional treatment group (control group, C group, n equal to 24). Patients in both groups received conventional treatment, including active treatment of the primary disease, respiratory support, nutritional support and fluid management therapy, while those in P group were given penehyclidine hydrochloride (1 mg, im, q. 12 h) in addition. The TLR4 expression of 20 healthy volunteers were detected. The clinical effect, average length of stay in ICU and hospital, values of PaO2 and PaO2/FiO2, expression of TLR4 on the surface of peripheral blood mononuclear cells and some serum cytokines were evaluated for 48 h.

RESULTSThe general conditions of the two groups were improved gradually and PaO2 increased progressively. Compared with 0 h, PaO2 and PaO2/FiO2 at 6, 12, 24 and 48 h after treatment were significantly increased (P less than 0.05). The improvement in P group was obviously greater than that in C group (P less than 0.05). The average length of hospitalization showed no difference between the two groups, but penehyclidine hydrochloride significantly decreased the average length of stay in ICU (t equal to 3.485, P less than 0.01). The expression of TLR4 in two groups were both obviously higher than that of healthy volunteers (P less than 0.01). It decreased significantly at 24 h (t equal to 2.032, P less than 0.05) and 48 h (t equal to 3.620, P less than 0.01) and was lower in P group than in C group. The patients who showed a higher level of TLR4 expression in early stage had a worse prognosis and most of them developed acute respiratory distress syndrome (ARDS). The incidence of ARDS was 23.8% in P group and 29.17% in C group at 24 h. Untill 48 h, there were other two patients developing ARDS in control group. Serum IL-1, IL-8 and TNF-alpha expressions reduced after 24 h in both groups. The reduction in P group was more obvious than that in C group (P less than 0.05). IL-13 increased gradually from 0 h to 24 h, and decreased slightly at 48 h, which showed no difference between two groups (t equal to 1.028, P larger than 0.05).

CONCLUSIONSPenehyclidine hydrochloride improves the arterial oxygen pressure, down-regulates the expression of TLR4 and restrains the inflammatory cytokines in the downstream of TLR4 signaling pathway. It prevents the development of ALI and can be considered as an important drug in ALI treatment.

Acute Lung Injury ; drug therapy ; etiology ; physiopathology ; Cytokines ; blood ; Heart Rate ; drug effects ; Humans ; Oxygen ; blood ; Prognosis ; Quinuclidines ; therapeutic use ; Toll-Like Receptor 4 ; genetics ; physiology

This study was aimed to shed light on the association of beta-adrenoceptor (beta-AR, includeing three subgroups: beta1, beta2 and beta3)gene polymorphism with resting heart rate (RHR). The RHRs of 150 healthy subjects (male 80; female 70) in the supine were detected by computerized system for analyzing the electrocardiosignals. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific-PCR techniques were used to determine Ser49Gly and Arg389Gly polymorphism of beta1-adrenoceptor gene; Arg16Gly and Gln27Glu polymorphism of beta2-adrenoceptor gene and Trp64Arg polymorphism of beta3-adrenoceptor gene; in these subjects. The results were as follows: The Arg389Gly polymorphism of beta1-adrenoceptor gene is significantly associated with RHR (P<0. 05), and the difference among three RHRs in male group is significantly higher than in group female group (P=0.0030 vs 0.0045). Individuals with Gly/Gly genotype have the highest RHR (male: 80.98+/-3.09; female: 84.23+/-6.28). No significant association was found among Ser49Gly, Arg16Gly, Gln27Glu and Trp64Arg polymorphism with RHR respectively (P> 0.05). RHR is associated with genotype. Arg389Gly polymorphism of beta1-adrenoceptor gene is significantly associated with RHRs, and the higher significant difference among male's RHRs,when compared with that among female's, suggests that male's RHRs be more influenced by genotype. Thus the clinical phenomenon of "the correlation of heart rate and mortality in male is higher than that in female" could be explained at the gene level.
Electrocardiography ; Female ; Heart Rate ; physiology ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Receptors, Adrenergic, beta ; genetics ; Signal Processing, Computer-Assisted

OBJECTIVETo investigate the effects of retroviral vector containing shRNA targeting rat angiotensin II type 1 receptor (AT1R) gene (Ad5-AT1R-shRNA) on blood pressure and AT1R mRNA expression in spontaneously hypertensive rats (SHR).

METHODSRetroviral vector containing shRNA targeting rat AT1R gene was constructed and propagated further in 293 cells. SHR rats were randomly divided into SHR + Ad5-AT1R-shRNA (1.7 x 10(9) TCID(50)/ml) group and SHR (Ad5-EGFP, 7.9 x 10(9) TCID(50)/ml, n = 11 each) and 11 male Wistar-Kyoto rats (WKY) serve as normal controls (Ad5-EGFP, 7.9 x 10(9) TCID(50)/ml). Systolic blood pressure was measured before and after single intravenous injection of Ad5-AT1R-shRNA or Ad5-EGFP. Heart, liver, kidney, aorta and adrenal gland were removed after blood pressure measurement. Tissue Ad5-AT1R-shRNA expression was detected with fluorescence microscope and AT1R mRNA in liver, kidney and aorta was measured by fluorescence quantitative PCR.

RESULTSAd5-AT1R-shRNA significantly reduced blood pressure compared with controls (-29 mm Hg, 1 mm Hg = 0.133 kPa, P < 0.05) 24 hours after single injection and this antihypertensive effect could last for 5 to 7 days. Ad5-AT1R-shRNA expression detected with fluorescence microscope was significantly increased in heart, liver, kidney, aorta and adrenal gland post Ad5-AT1R-shRNA injection. AT1R mRNA in kidney and aorta (0.086 +/- 0.014, 0.051 +/- 0.023) were significantly decreased in Ad5-AT1R-shRNA treated rats compared with SHR control rats (0.362 +/- 0.042, 0.463 +/- 0.045, P < 0.01).

CONCLUSIONThe results indicate that Ad5-AT1R-shRNA could inhibit the tissue AT1R mRNA expression and produce prolonged antihypertensive effects in SHR rats.

Adenoviridae ; Animals ; Blood Pressure ; Genetic Vectors ; Heart Rate ; Hypertension ; genetics ; metabolism ; physiopathology ; Male ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Receptor, Angiotensin, Type 1 ; genetics ; metabolism