DNA was extracted from the peripheral venous blood of 338 subjects using BLOOD DNA MINI KIT. The 5 site SNP in 3 subtypes of Beta-AR were genotyped by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and allele-specific primer PCR techniques. The genotypes combination distribution of SNP at 5 sites in the 3 subtypes of Beta-AR were determined by clustering analysis technique. The natural combination distribution characteristics for SNP at 5 sites in the 3 subtypes of Beta-AR in 338 subjects were obtained. Sixty-seven combinations types were found. The preceding 5 combinations in the natural combination distribution of the SNP were: (1) The genotype combination of forty subjects was B1-AR S/S49+B1-AR R/R389+B2-AR R/G16+B2-AR Q/E27+B3-AR W/W64, its probability was 11.83%. (2) The genotype combination of thirty-three subjects was B1-AR S/S49+B1-AR R/R389+B2-AR R/G16+B2-AR Q/Q27+B3-AR W/W64, its probability was 9.76%. (3) The genotype combination of nineteen subjects was B1-AR S/S49+B1-AR R/G389+B2-AR R/G16+B2-AR Q/Q27+B3-AR W/W64, its probability was 5.62%. (4) The genotype combination of sixteen subjects was B1-AR S/S49+B1-AR R/G389+B2-AR R/G16+B2-AR Q/E27+B3-AR W/W64, its probability was 4.74%. (5) The genotype combination of thirteen subjects was B1-AR S/G49+B1-AR R/R389+B2-AR R/G16+B2-AR Q/E27+B3-AR W/W64, its probability was 3.85%. The obvious correlations exist among full sample and female or male subgroup, and between female and male subgroups.
Adult ; Aged ; Aged, 80 and over ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; methods ; Polymorphism, Single Nucleotide ; genetics ; Receptors, Adrenergic, beta ; classification ; genetics ; Receptors, Adrenergic, beta-1 ; genetics ; Receptors, Adrenergic, beta-2 ; genetics ; Receptors, Adrenergic, beta-3 ; genetics

OBJECTIVETo investigate the alteration of expressions of beta(1)-, beta(2)-, beta(3)-adrenoceptor mRNA in human myocardial tissue and the relation between their expressions and cardiac function in patient with heart failure.

METHODSThe mRNA expressions of beta(1)-, beta(2)- and beta(3)-adrenergic receptors in myocardial tissue were analyzed by using the reverse transcriptase-polymerase chain reaction in 24 patients with heart failure of valvular heart disease and 5 control subjects.

RESULTSBeta(1)-adrenergic receptor mRNA expressions in myocardium were significantly lower in patients with heart failure than those in control subjects, and progressively reduced with aggravation of heart function. By contrast, beta(3)-adrenoceptor mRNA expressions were significantly higher in patients with heart failure than those in controls, and progressively elevated with aggravation of cardiac function. No difference was observed in beta(2)-adrenergic receptor among all groups.

CONCLUSIONThe changes of beta-adrenergic receptor mRNA expression are associated with the severity of heart failure.

Adult ; Case-Control Studies ; Female ; Heart Failure ; genetics ; metabolism ; physiopathology ; Humans ; Male ; Middle Aged ; RNA, Messenger ; metabolism ; Receptors, Adrenergic, beta-1 ; genetics ; metabolism ; Receptors, Adrenergic, beta-2 ; genetics ; metabolism ; Receptors, Adrenergic, beta-3 ; genetics ; metabolism

OBJECTIVETo explore the changes on the content of substrate, the activity of correlative enzyme and the mRNA and protein expressions of beta(3)-adrenoceptor and peroxisome proliferator-activated receptor alpha (PPARalpha) in human failing heart.

METHODPapillary muscles from 20 patients with heart failure during mitral valves replacement and 6 control subjects died of non-cardiac accidents were obtained and free fat acid (FFA), lactic acid (LD) and the activity of Na(+)K(+)-ATPase and Ca(2+)Mg(2+)-ATPase, protein and mRNA expressions of beta(3)-adrenergic receptor and PPARalpha were measured.

RESULTIn the failing heart, the contents of fat acid, LD and expression of beta(3)-adrenoceptor mRNA and protein were significantly higher while the activity of Na(+)K(+)-ATPase and Ca(2+)Mg(2+)-ATPase, expressions of PPARalpha at mRNA and protein levels were significantly lower than those in control myocardium.

CONCLUSIONMetabolic remodeling (upregulation of beta(3)-adrenoceptor and downregulation of PPARalpha) might contribute to the pathophysiology of heart failure.

Adult ; Female ; Heart Failure ; metabolism ; Humans ; Male ; Middle Aged ; Myocardium ; metabolism ; PPAR alpha ; metabolism ; Receptors, Adrenergic, beta-3 ; metabolism

AIMTo evaluate the effects of beta3-adrenergic receptors (ARs) agonist (BRL-37344) on beating rate and cAMP levels and investigate the influence on the chronotropic action of beta3-ARs in cultured cardiomyocyte of rats.

METHODSCultured neonatal rat cardiomyocytes were divided randomly into eight groups, control group, ISO group, Nadolol + ISO group, BRL group, PIX + BRL group, L-NAME + BRL group, Nadolol + BRL group and Bupranolol + BRL group. Beating rate of culture neonatal rat cardiomyocytes was observed and cAMP measured by enzyme immunoassay kit. Expression levels of beta3-ARs mRNA in cardiomyocytes was evaluated by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSISO, nonspecific beta-ARs agonist increased beating rate and intracellular cAMP production, antagonized by Nadolol, beta1, beta2-ARs antagonist. BRL37344 decreased beating rate and intracellular cAMP levels. FPTX, Gi protein inhibitor and Bupranolol, nonspecific beta-ARs antagonist totally blocked the effect and L-NAME, nitric oxide synthase (NOS) inhibitor partly blocked the effect, but Nadolol did not. There was the expression of beta3-AR mRNA in cardiomyocytes by RT-PCR.

CONCLUSIONSBeta3-ARs showed in cardiomyocytes and produced negative chronotropic effects. beta1, beta2-ARs antagonist did not affect it. It suggested beta3-ARs signal transduction was related with G1 protein. The negative inotropic effect of beta3-ARs stimulation was mediated by activation of the NOS pathway.

Adrenergic beta-Agonists ; pharmacology ; Animals ; Animals, Newborn ; Cells, Cultured ; Cyclic AMP ; metabolism ; Ethanolamines ; pharmacology ; Myocytes, Cardiac ; drug effects ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; Receptors, Adrenergic, beta-3 ; metabolism

BACKGROUNDStimulation of the heart beta 3-adrenoceptor (AR) may result in a negative inotropic effect. Being up-regulated, beta 3-AR plays a more important role in the regulation of cardiac function during heart failure. However, the effect of chronic blocking of beta 3-AR on heart failure has not been fully elucidated. In this study, we used a selective beta 3-AR antagonist SR59230A to treat a well defined heart failure rat model chronically, then evaluated its effect on cardiac function and investigated the mechanism.

METHODSMale Wistar rats were chosen randomly as controls (n = 8). Isoproterenol induced heart failure rats were randomly divided into ISO group (n = 10) and SR group (n = 10). The ISO group received intraperitoneal injection of 1 ml saline twice a day; the SR group received intraperitoneal injection of SR59230A 85 nmol in 1 ml saline twice a day; and the control group received no treatment. The treatment was started 24 hours after the last isoproterenol injection and continued for 7 weeks. Then we measured the following indexes: the ratio of heart weight to body weight (HW/BW) and the ratio of left ventricular weight to body weight (LVW/BW), collagen volume fraction (CVF), left ventricular end diastolic dimension (LVEDd), left ventricular end systolic dimension (LVESd), ejection fraction (EF), fractional shortening (FS) and the ratio of E wave to A wave (E/A), the mRNA and protein expression of beta 3-AR and eNOS, and cGMP level in the heart.

RESULTSThe ratios HW/BW and LVW/BW were significantly increased in the ISO group compared with the control group (P < 0.01), but they were limited in the SR group (P < 0.05 compared with the ISO group). CVF increased in the ISO group and the SR group (P < 0.01), but it was significantly attenuated in the SR group (P < 0.01). LVEDd, LVESd and E/A ratio were significantly increased in the ISO group compared with the control group (P < 0.01), while EF and FS were significantly decreased (P < 0.01). Compared with the ISO group, the SR group showed that LVEDd, LVESd and E/A ratio were significantly decreased (P < 0.01), whereas EF and FS were significantly increased (P < 0.01). beta(3)-AR and eNOS mRNA and protein in the ISO group were significantly increased when compared with the control group (P < 0.01). These increases were all attenuated in the SR group compared with the ISO group (P < 0.01). The level of cGMP in myocardial tissue was significantly increased in the ISO group compared with the control group (P < 0.01), whereas SR59230A treatment normalized this increment (P < 0.01).

CONCLUSIONSChronic blocking of beta 3-AR could ameliorate cardiac function in heart failure rats and its mechanism involves inhibition of the negative inotropic effect and attenuation of cardiac remodeling.

Adrenergic beta-3 Receptor Antagonists ; Adrenergic beta-Antagonists ; pharmacology ; therapeutic use ; Animals ; Blotting, Western ; Disease Models, Animal ; Echocardiography ; Enzyme-Linked Immunosorbent Assay ; Heart Failure ; drug therapy ; physiopathology ; Male ; Myocardium ; pathology ; Nitric Oxide Synthase Type III ; genetics ; Propanolamines ; pharmacology ; Rats ; Rats, Wistar ; Receptors, Adrenergic, beta-3 ; physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Ventricular Function, Left ; drug effects

PURPOSE: This research was conducted to provide basic information about the effects of aerobic exercise on physiological change in middle-aged obese women according to differences of beta3-adrenergic receptor polymorphisms. METHOD: Twenty-nine middle aged obese women with over 30%BMI were divided into three groups according to beta3-adrenergic receptor gene polymorphism[Variable Group(VG):9, Normal Group(NG):10, Control Group(CG):10]. The VG and NG groups performed walking at 50% exercise intensity for 30 minutes a day, 4 days a week, for 12 weeks. The data was analyzed using the SPSS program. RESULT: The level of leptin, insulin and % body fat in the VG and NG groups was significantly lower than those of the CG after 12 weeks. In addition, the level of HDL-C in the VG and NG was significantly higher than that of the CG after 12 weeks. However, TC, TG and body weight between groups didn't appear significant at the end of 12 weeks. CONCLUSIONS: Aerobic exercise didn't cause differences in persons with differing beta3-adrenergic receptor gene polymorphisms, but aerobic exercise affected the physiological change in middle-aged obese women. The findings suggest that aerobic exercise is a desirable nursing intervention for obesity control in middle-aged obese women.
Adult ; *Body Composition ; *Exercise ; Female ; Humans ; Insulin/*blood ; Leptin/*blood ; Lipids/*blood ; Middle Aged ; Obesity/blood/*physiopathology ; *Polymorphism, Genetic ; Receptors, Adrenergic, beta-3/*genetics

OBJECTIVETo understand the influence of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and beta3-adrenergic receptor (beta3-AR) gene Trp64Arg polymorphism on fetal growth and neonatal insulin sensitivity.

METHODSTotally 296 newborn infants were selected into our study and divided into 2 groups according to gestational age and birth weight: adequate-for-gestational-age (AGA) group (222 cases) and small-for-gestational-age (SGA) group (74 case). Serum glucose and insulin were examined in the morning of the 3rd day before milk. Insulin sensitivity was evaluated by homeostasis model assessment (HOMA) equation. beta3-AR gene Trp64Arg polymorphism and ACE gene I/D polymorphism (202 cases) were analysed using polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) technique. Gestational age, birth weight, birth weight percentage, serum glucose, insulin and HOMA-IR were compared among different genotype groups. Statistical analysis was performed with the SPSS 10.0 software.

RESULTSNo significant difference was found between the serum glucose level of SGA group (4.03 +/- 1.05 mmol/L) and AGA group (4.05 +/- 1.14 mmol/L), P = 0.008. The serum insulin level (converted into Ln) of SGA group (2.262 +/- 0.746) was significantly higher than that of AGA group (1.757 +/- 0.805), P < 0.001. The HOMA-IR (also converted into Ln) level of SGA group (0.217 +/- 0.367) was also significantly higher than that of AGA group (0.001 +/- 0.378), P < 0.001. In the SGA group beta3-AR gene Arg64 allele carriers had higher serum insulin and HOMA-IR level (both changed to Ln, 2.654 +/- 0.701, 0.371 +/- 0.338) compared with noncarriers (2.074 +/- 0.698, 0.143 +/- 0.360), P < 0.05. The ACE gene DD genotype carriers had higher serum insulin and HOMA-IR level (both were converted into Ln, 2.19 +/- 0.91, 0.51 +/- 1.01) compared with II (1.77 +/- 0.85, 0.02 +/- 0.93) and ID genotype group (1.77 +/- 0.83, 0.05 +/- 0.91), P < 0.05. The ACE gene DD carriers had lower birth weight percentage compared with II and ID genotype group, P < 0.05. When both genes' polymorphisms were taken into account, the newborns who had both DD genotype and Arg64 allele had obviously higher serum insulin level (Ln, 2.560 +/- 1.160) than the neonates who had only one of the polymorphisms mentioned above (1.970 +/- 0.821, 1.992 +/- 0.706) and the neonates who had neither of the two polymorphisms (1.683 +/- 0.832), P < 0.05. The newborns who had both DD genotype and Arg64 allele also had significantly higher HOMA-IR level (Ln, 1.042 +/- 1.315) than the neonates who had only one of the polymorphisms mentioned above (0.247 +/- 0.710, 0.230 +/- 0.890) and the neonates who had neither of the two polymorphisms (-0.053 +/- 0.924), P < 0.05.

CONCLUSIONNewborns SGA had impaired insulin sensitivity. beta3-AR gene Trp64Arg polymorphism and ACE gene I/D polymorphism are important factors that may connect IUGR with insulin resistance syndrome in adulthood.

Female ; Fetal Development ; genetics ; Humans ; INDEL Mutation ; Infant, Newborn ; Infant, Small for Gestational Age ; Insulin Resistance ; Male ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; Receptors, Adrenergic, beta-3 ; genetics

OBJECTIVETo investigate the additive effects of uncoupling protein 2 (UCP2) gene Ala55Val variation and ADR beta(3) gene Trp64Arg variation on the obesity in Chinese Han population.

METHODSThe UCP2 gene Ala55Val variation and ADR beta(3) gene Trp64Arg variation were examined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) in 119 obese subject with mean BMI (27.9+/-2.98)kg/m(2) and in 177 control subjects with mean BMI(21.9+/-1.9)kg/m(2). The additive effects of the two gene mutations were analyzed.

RESULTS(1) The frequency of ADR beta(3) gene Trp64Arg variation in obese subjects was not significantly different from that in control subjects. In control subjects, the Trp64Arg variation carriers had higher fasting glucose level and 2-hour-post-prandial glucose level than did non-carriers. (2) The frequency of homozygote of UCP2 gene Ala55Val variation in obese subjects was higher than that in the control subjects (OR=3.71, P=0.001). In control subjects the Ala55Val variation carriers had higher BMI. (3) When there was only UCP2 gene or ADR beta(3) gene mutation, the frequency of gene mutation in obese subjects was not significantly different from that in control subjects (P>0.05). But when there were simultaneously two gene mutations, the frequency of gene mutations was higher in obese subjects than in control subjects (OR=2.57, P=0.009). (4) The genotype carriers with Val/Val+ Trp/Arg were the greatest relation to obese obesity (OR=8.58, P=0.002).

CONCLUSIONThe homozygote of UCP2 gene Ala55Val mutation increases the risk of obesity. Though the UCP2 gene mutation alone or the ADR beta(3) gene mutation alone is not associated with obesity, the possible additive effects of the two micro-genes increase the occurring of obesity.

Adult ; Aged ; Female ; Humans ; Ion Channels ; Male ; Membrane Transport Proteins ; genetics ; Middle Aged ; Mitochondrial Proteins ; genetics ; Mutation ; Obesity ; genetics ; Receptors, Adrenergic, beta-3 ; genetics ; Uncoupling Protein 2

OBJECTIVETo study the effect of beta3 adrenergic receptor (beta3AR) Trp64Arg and peroxisome proliferator activated receptor gamma 2 (PPARgamma2) Prol2Ala polymorphisms on insulin resistance.

METHODSOne hundred and eight dizygotic twin pairs were enrolled in this study. Microsatellite polymorphism was used to diagnose zygosity of twins. Insulin sensitivity was estimated with logarithm transformed homeostasis model assessment (HOMA). PCR-RFLP analysis was performed to detect the variants. As a supplement to the sib-pair method, identity by state (IBS) was used to analyze the association of polymorphisms with insulin sensitivity.

RESULTSThe genotype frequencies of Trp64Trg, Trp64Arg, and Arg64Arg were 72.3%, 23.8%, and 3.9%, respectively, while the genotype frequencies of Prol2Pro, Prol2Ala, and Alal2Ala were 89.9%, 9.6%, and 0.5%, respectively. For beta3AR Trp64Arg the interclass co-twin correlations of Waist-to-hip ratio (WHR), blood glucose (GLU), and insulin (INS), homeostasis model assessment insulin resistance index (HOMA-IR) of the twin pairs sharing 2 alleles of IBS were greater than those sharing 0-1 allele of IBS, and HOMA-IR had statistic significance. For PPARgamma2 Pro12Ala most traits of twin pairs sharing 2 alleles of IBS had greater correlations and statistic significance in body mass index (BMI), WHR, percent of body fat (PBF) and GLU, but there were low correlations of either insulin or HOMA-IR of twin pairs sharing 1 or 2 alleles of IBS. The combined effects of the two variations showed less squared significant twin-pair differences of INS and HOMA-IR among twins sharing 4 alleles of IBS.

CONCLUSIONSBeta3AR Trp64Arg and PPARgamma2 Pro12Ala polymorphisms might be associated with insulin resistance and obesity, and there might be slight synergistic effects between this two gene loci, and further studies are necessary to confirm this finding.

Adolescent ; Child ; Child, Preschool ; Genotype ; Humans ; Insulin Resistance ; genetics ; Obesity ; genetics ; PPAR gamma ; genetics ; Polymorphism, Genetic ; Receptors, Adrenergic, beta-3 ; genetics ; Twins, Dizygotic ; genetics ; metabolism

BACKGROUNDIt has been shown that the &beta;3-adrenergic receptor (&beta;3-AR) gene Trp64Arg mutation was closely related to obesity and insulin resistance, and may be related to the prevalence of metabolic syndrome (MS). The aim of this study was to investigate the relationship between the &beta;3-AR gene mutation and the prevalence of MS.

METHODSA seven-year follow-up study was initiated in 2000, with 496 samples of simplex obese subjects (body mass index ≥ 25 kg/m(2)) and 248 normal-weight subjects. According to the &beta;3-AR genotypes, the subjects were classified as Trp64 homozygote group and Arg64 carrier group and after 7 years the prevalence of MS was determined.

RESULTSAccording to the baseline profile, there were no significant differences in the adiposity, blood pressure, lipid profile, fasting plasma glucose and fasting insulin between Trp64 homozygote group and Arg64 carrier group either in obesity or normal-weight subjects. The results of follow-up study indicated that in obese men the prevalence rate of MS was much higher in Arg64 carrier group than that in Trp64 homozygote group (54.76% vs. 40.85%, P < 0.05), but there was no statistical difference in women of the above groups. The prevalence rate of MS in obese men of both Trp64 homozygote group and Arg64 carrier obese group were obviously higher than that in women of the above groups (40.85% vs. 18.27% and 54.76% vs 21.28%, all P < 0.005). Differences were not statistically significant in the prevalence of MS for normal weight Trp64 homozygote group and normal weight Arg64 carrier group, either between men, between women, or between men and women. Comparison of populations indicated that no matter with the &beta;3-AR gene mutation or not, the prevalence of MS in obese subjects was significantly higher than normal weight subjects (χ(2) = 28.240 and χ(2) = 15.586, all P < 0.005). Logistic analysis showed that the mutation of &beta;3-AR gene was associated with the prevalence of MS in men.

CONCLUSIONThe mutation of &beta;3-AR gene is the independent risk factor for the prevalence of MS in men.

Adult ; Body Mass Index ; Female ; Follow-Up Studies ; Humans ; Insulin Resistance ; Logistic Models ; Male ; Metabolic Syndrome ; etiology ; genetics ; Middle Aged ; Mutation ; Receptors, Adrenergic, beta-3 ; genetics