1.Genotype combination distribution of 5-site SNPs in 3 subtypes of beta adrenoceptor.
Zhengxiang XIE ; Yonghong NIU ; Houxun MA ; Zhangyong LI ; Yuehui YIN
Journal of Biomedical Engineering 2005;22(1):99-103
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
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Aged
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Aged, 80 and over
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Female
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Genotype
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Humans
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Male
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Middle Aged
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Polymerase Chain Reaction
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methods
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Polymorphism, Single Nucleotide
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genetics
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Receptors, Adrenergic, beta
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classification
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genetics
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Receptors, Adrenergic, beta-1
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genetics
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Receptors, Adrenergic, beta-2
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genetics
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Receptors, Adrenergic, beta-3
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genetics
3.The relationship between expressions of beta1-, beta2-, beta3-adrenoceptor mRNA of myocardium and cardiac function in patients with heart failure.
Zhen-kui LI ; Shan-jun ZHU ; Lin-jun YU ; Ying TIAN ; Yi-zhong ZHOU ; Jiang WANG
Chinese Journal of Cardiology 2005;33(4):351-353
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
4.Distinct beta-adrenergic receptor subtype signaling in the heart and their pathophysiological relevance.
Ming ZHENG ; Qi-De HAN ; Rui-Ping XIAO
Acta Physiologica Sinica 2004;56(1):1-15
In the heart, stimulation of beta-adrenergic receptors (betaAR) serves as the most powerful means to increase cardiac contractility and relaxation in response to stress or a "fight-or-flight" situation. However, sustained beta-adrenergic stimulation promotes pathological cardiac remodeling such as myocyte hypertrophy, apoptosis and necrosis, thus contributing to the pathogenesis of chronic heart failure. Over the past decade, compelling evidence has demonstrated that coexisting cardiac betaAR subtypes, mainly beta(1)AR and beta (2)AR, activate markedly different signaling cascades. As a result, acute beta(1)AR stimulation activates the G(s) -adenylyl cyclase-cAMP-PKA signaling that can broadcast throughout the cell, whereas beta(2)AR-evoked cAMP signaling is spatially and functionally compartmentalized, due to concurrent G(i) activation. Chronic stimulation of beta(1)AR and beta(2)AR elicits opposing effects on the fate of cardiomyocytes: beta(1)AR induces hypertrophy and apoptosis; but beta(2)AR promotes cell survival. The cardiac protective effect of beta(2)AR is mediated by a signaling pathway sequentially involving G(i), G(betagamma), PI3K and Akt. Unexpectedly, beta(1)AR-induced myocyte hypertrophy and apoptosis are independent of the classic cAMP/PKA pathway, but require activation of Ca(2+)/calmodulin-dependent kinase II (CaMK II). The outcomes of cardiac-specific transgenic overexpression of either beta AR subtype in mice have reinforced the fundamentally different functional roles of these betaAR subtypes in governing cardiac remodeling and performance. These new insights regarding betaAR subtype stimulation not only provide clues as to cellular and molecular mechanisms underlying the beneficial effects of beta AR blockers in patients with chronic heart failure, but also delineate rationale for combining selective beta(1)AR blockade with moderate beta(2)AR activation as a potential novel therapy for the treatment of chronic heart failure.
Adenylyl Cyclases
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metabolism
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Animals
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Cyclic AMP-Dependent Protein Kinases
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metabolism
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GTP-Binding Proteins
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metabolism
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Heart
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physiology
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Heart Failure
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physiopathology
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Humans
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Myocardium
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metabolism
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Receptors, Adrenergic, beta
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classification
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physiology
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Receptors, Adrenergic, beta-1
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physiology
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Receptors, Adrenergic, beta-2
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physiology
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Signal Transduction
5.Study of autoantibodies against the G-protein-coupled beta 2- and alpha 1-adrenergic and AT1 receptors in patients with primary hypertension.
Lin ZHANG ; Liang CUI ; Guo-bin MIAO ; Wen-shu ZHAO ; Shu-yan WANG ; Xiu-lan LIU
Acta Academiae Medicinae Sinicae 2002;24(4):367-369
OBJECTIVETo determine whether autoantibodies against the cardiac G-protein-coupled beta 2- and alpha 1-adrenergic and AT1 receptors are related to patients with primary hypertension.
METHODSSynthetic peptides corresponding to amino acid sequences of the second extracellular loops of the beta 2- and alpha 1-adrenergic and AT1 receptors were respectively used as antigens to screen sera from patients with hypertensive heart diseases (n = 50) as well as simple hypertension (n = 40) and healthy blood donors (n = 40) using ELISA test.
RESULTSThe positive ratio of autoantibodies against beta 2 and alpha 1 and AT1 receptors in patients with hypertensive heart diseases were significantly higher than patients with simple hypertension and healthy donors. The geometric mean titers of autoantibodies against beta 2- and alpha 1-adrenergic and AT1 receptors had no difference between the patients with hypertensive heart diseases and the patients with simple hypertension, but the geometric mean titers of two groups were higher than healthy donors. In the patients with hypertensive heart diseases, 81.0% of the patients with autoantibodies against beta 2-adrenergic receptor had autoantibodies against alpha 1-adrenergic receptor and 76.2% had autoantibodies against AT1 receptors. The percent of the autoantibodies against three receptors in patients with hypertensive heart diseases were 52.4%.
CONCLUSIONSAutoantibodies against beta 2- and alpha 1-adrenergic and AT1 receptors play an important role in the pathophysiological changes of primary hypertension, and may participate myocardial and vessel remodeling.
Adult ; Aged ; Autoantibodies ; blood ; Female ; Humans ; Hypertension ; immunology ; Male ; Middle Aged ; Receptor, Angiotensin, Type 1 ; immunology ; Receptors, Adrenergic, alpha-1 ; immunology ; Receptors, Adrenergic, beta-2 ; immunology
6.Effects of exhaustive exercise on contractile responses mediated by beta-adrenoceptor in rat cardiac myocytes.
Li-Ping GAO ; Ying LIU ; Hong SUN
Chinese Journal of Applied Physiology 2013;29(5):437-440
OBJECTIVETo investigate the effects of exhaustive exercise on contraction mediated by beta-adrenoceptor (beta-AR) in rat cardiac myocytes and to analyze the mechanism by which cardiac systolic dysfunction is caused after exhaustive exercise.
METHODSSixteen SD rats were divided randomly into sedentary group and trained group. Cardiac myocytes were isolated from sedentary group and trained group after five times of exhaustive exercise in one week. Shortening response to norepinephrine (NE), time-to-peak contraction (TTP) and time-to-95% relaxation (R95) were measured after alpha1-AR were blocked. Also shortening responses to different levels of NE were observed.
RESULTSShortening amplitudes in trained rat cardiomyocytes were lower than that in sedentary group. Compared with sedentary group, shortening amplitudes induced by beta-AR stimulation were significantly decreased, meanwhile TTPs and R95 were prolonged when beta-AR were activated in trained rat cardiomyocytes. beta-AR responsiveness to NE was weakened in trained group compared with that in sedentary group.
CONCLUSIONDecreased shortening cardiomyocyte systolic function stimulating by beta-AR could result in cardiac systolic dysfunction after exhaustive exercise.
Animals ; Male ; Myocardial Contraction ; Myocytes, Cardiac ; physiology ; Physical Conditioning, Animal ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta-1 ; blood
7.Presence of autoantibodies against β1-adrenoceptor aggravates the kidney injury in rats.
Lin ZUO ; ; Rui ZHAO ; Li WANG ; Ding-Chao LV ; Shan-Hui SHI ; Ke WANG ; Xiao LI ; Ting-Ting LV ; Rong-Rui ZHAO ; Hui-Rong LIU
Acta Physiologica Sinica 2014;66(2):175-185
Since the autoantibodies against the second extracellular loop of β(1)-adrenoceptor (β(1)-AABs) have been found in the sera of patients with idiopathic dilated cardiomyopathy (IDCM), the involvement of autoimmune mechanisms in the pathogenesis of many cardiovascular diseases has extensively been investigated. Our previous study found that urinary occult blood and protein excretion were frequently found in the rats with positive β(1)-AABs, but the mechanisms are unclear. Therefore, we infused the β(1)-AABs into the vein periodically in an attempt to investigate whether β(1)-AABs could induce morphological and functional changes in the kidneys of adult and aged rats and explore the possible mechanisms. The synthetic peptide according to the sequences of the second extracellular loop of β(1)-adrenoceptor (β(1)-AR-ECII) was used to immunize the adult rats to acquire enough β(1)-AABs for use. Neonatal rat ventricular myocytes (NRVMs) culture was used to observe the biological effects of β(1)-AABs on the beating rate. The purified β(1)-AABs were transfused into the vein of rats. The sera level of blood urea nitrogen (BUN), creatinine (CR), uric acid (UA), urinary specific gravity, protein excretion, occult blood and urinary glucose were detected at the different time points by biochemistry and urine analyzers. HE and Masson's trichrome staining were used to detect the changes in kidney structure of passively immunized rats. Enhanced green fluorescent protein (EGFP) and β(1)-AR-EGFP plasmids were transfected into the human embryonic kidney 293 (HEK293) cells in order to observe the changes in cell injury with the treatment of β(1)-AABs. It was found that the sera level of BUN, CR and UA increased gradually and the ratio of BUN to CR decreased progressively with the administration of β(1)-AABs. The increasing of proteinuria, urinary occult blood and urinary glucose was detected by urine analyzer in β(1)-AABs group. By HE and Masson's coloration, lots of mononuclear cell infiltration and collagen fibers deposition could be observed at the 24th week of immunization. After the treatment of β(1)-AABs, the caspase-3 activity increased significantly in the HEK293 cells transfected with β(1)-AR-EGFP plasmids, while no significant changes were observed for lactate dehydrogenase (LDH) activity. The results indicate that long-term presence of β(1)-AABs can induce the morphological and functional damage of the kidneys in adult and aged rats.
Acute Kidney Injury
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immunology
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physiopathology
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Animals
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Autoantibodies
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immunology
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HEK293 Cells
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Humans
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Myocytes, Cardiac
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physiology
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Rats
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Receptors, Adrenergic, beta-1
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immunology
8.Effects of norepinephrine on the proliferation and activation of rat hepatic stellate cells.
Qiao YANG ; Yao-wen ZHANG ; Hong-yan LIU ; Yu-hu SONG ; Wang-xian TANG
Chinese Journal of Hepatology 2008;16(11):844-848
OBJECTIVETo elucidate the relationship between rat hepatic stellate cells (HSC) and sympathetic neurotransmitter norepinephrine (NE) during liver fibrosis.
METHODSUsing immunofluorescence and RT-PCR, the expressions of a1 and b2-adrenoceptors in activated HSC were detected. Methyl thiazolyl tetrazolium (MTT) was adopted to investigate the effect of NE on the proliferation of HSC. Meanwhile, the expressions of collagen-1, transforming growth factor beta (TGFb) and smooth muscle a-actin (a-SMA) in NE-stimulated HSC were detected by RT-PCR. The contents of NE in HSC were determined by high performance liquid chromatography-electrochemical detector (HPLC-ECD).
RESULTSThe a1 and b2-adrenoceptors were expressed in HSC. NE markedly stimulated the proliferation of HSC in a concentration-dependent manner (F = 140.464, P less than 0.05). NE induced the mRNA expressions of collagen-1, TGFb and a-SMA in HSC (t= -4.160; t= -8.763; t= -17.651, P less than 0.05). HSC were synthesizing and releasing NE, especially when stimulated with platelet-derived growth factor (PDGF) (10 ng/ml) (t= -32.907, P less than 0.05).
CONCLUSIONOur findings show that HSC are direct targets of NE and HSC are hepatic neuroglial cells that produce and respond to sympathetic neurotransmitter norepinephrine, suggesting that interrupting sympathetic nervous system signaling may be useful in the treatment of liver fibrosis.
Actins ; metabolism ; Animals ; Cell Proliferation ; drug effects ; Cells, Cultured ; Collagen Type I ; metabolism ; Hepatic Stellate Cells ; drug effects ; metabolism ; Liver Cirrhosis ; Norepinephrine ; pharmacology ; Rats ; Receptors, Adrenergic, alpha-1 ; metabolism ; Receptors, Adrenergic, beta-2 ; metabolism ; Transforming Growth Factor beta ; metabolism
9.Beta2-adrenoceptor gene variant Arg16Gly is associated with idiopathic ventricular outflow-tract tachycardia.
Yu-qin RAN ; Ning LI ; Ying YANG ; Jing-zhou CHEN ; Li FENG ; Shu ZHANG ; Jie-lin PU
Chinese Medical Journal 2010;123(17):2299-2304
BACKGROUNDImbalance of the sympathetic nervous system was involved in the pathogenesis of idiopathic ventricular outflow-tract tachycardia (IVOT). We aimed to investigate whether the major genetic variants in β(1)- and β(2)-adrenoceptors and GNB3 C825T were associated with IVOT and verapamil sensitive idiopathic left ventricular tachycardia (ILVT).
METHODSPatients with IVOT and ILVT from December 2005 to December 2007 were consecutively enrolled into this study. Controls were randomly selected from the community-based inhabitants. Five genetic variants, Ser49Gly and Gly389Arg in the β(1)-adrenoceptor, Arg16Gly and Gln27Glu in the β(2)-adrenoceptor and GNB3 C825T, were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis.
RESULTSA total of 227 patients with IVOT and 110 patients with ILVT were included. Genotyping revealed that the 16Gly allele of Arg16Gly variant of β(2)-adrenoceptor was associated with a higher risk of IVOT (OR: 1.40, 95%CI: 1.12 - 1.75, P = 0.003 in the addictive model and OR: 1.62, 95%CI: 1.14 - 2.31, P = 0.007 in the dominant model). Patients with Gly16Gln27 haplotype also had a higher risk of IVOT (OR: 1.38, 95%CI: 1.11 - 1.73, P = 0.012). Other four variants, including Ser49Gly and Arg389Gly in β(1)-adrenoceptor, Gln27Glu in β(2)-adrenoceptor and GNB3 C825T, did not differ between patients with IVOT and controls. In patients with ILVT, no significant difference was found in these five variants compared with controls.
CONCLUSIONSArg16Gly in β(2)-adrenoceptor is significantly associated with IVOT in Chinese Han population. Major genetic variants in β(1)- and β(2)-adrenoceptor and GNB3 C825T may not be associated with ILVT. These data suggest a different arrhythmogenic mechanism in IVOT and ILVT.
Adult ; Genetic Predisposition to Disease ; Genetic Variation ; Genotype ; Haplotypes ; Humans ; Male ; Middle Aged ; Receptors, Adrenergic, beta-1 ; genetics ; Receptors, Adrenergic, beta-2 ; genetics ; Sex Characteristics ; Tachycardia, Ventricular ; genetics ; Ventricular Function
10.Association of β-adrenergic receptor genes polymorphisms with incidence of subsequent cardiovascular events in Han Chinese patients with coronary artery disease.
Zhi-Gen LI ; Hong WU ; Ying-Ling ZHOU ; Zhu-Jun CHEN ; Jin-Xiu MENG ; Jun-Qing YANG ; Ji-Yan CHEN ; Shi-Long ZHONG
Chinese Medical Journal 2013;126(24):4679-4684
BACKGROUNDSequence variants in the β-adrenergic receptor (ADRB) genes have a close relationship with the development of coronary artery disease (CAD) and the patient's prognosis. However, there is a lack of data on the role of the variants in ADRBs genes in Han Chinese patients with CAD. We aimed to investigate the association of genetic variants in the ADRB1 and ADRB2 genes with the incidence of major adverse cardiac event (MACE) in Han Chinese patients with CAD.
METHODSA total of 545 Han Chinese patients with CAD undergoing percutaneous coronary intervention (PCI) were recruited to the study and followed for one year. Three variant sites in ADRB1 (rs1801253) and ADRB2 (rs1042713 and rs1042714) were genotyped. The effect of the ADRB1 and ADRB2 genotypes on MACE within one year was assessed.
RESULTSThere were 47 cases of MACE during follow-up. There was no significant difference in the incidence of MACE among patients carrying different genotypes of the three variants in ADRB1 and ADRB2 (Log-rank, all P > 0.05). Cox regression analysis showed no association between three variants in ADRB1 and ADRB2 genes and the incidence of MACE during one-year follow-up, the adjusted hazard ratios (95% confidence interval) for rs1801253, rs1042713 and rs1042714 were 1.05 (0.54-2.02), 1.24 (0.58-2.64) and 1.66 (0.81-3.42), respectively.
CONCLUSIONOur data did not support a relationship between the three polymorphisms of ADRB1 (rs1801253) and ADRB2 (rs1042713 and rs1042714) genes and risk of subsequent cardiovascular events after PCI in Han Chinese patients with CAD.
Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; genetics ; Coronary Artery Disease ; genetics ; Female ; Genotype ; Humans ; Incidence ; Male ; Middle Aged ; Polymorphism, Genetic ; genetics ; Polymorphism, Single Nucleotide ; genetics ; Receptors, Adrenergic, beta ; genetics ; Receptors, Adrenergic, beta-1 ; genetics ; Receptors, Adrenergic, beta-2 ; genetics