Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study focused on 3 genetic polymorphisms that have previously been implicated in hypertension: the alpha-adducin (ADD1/Gly460Trp), beta1-adrenoreceptor (ADRB1/Arg389Gly), and G-protein beta3 subunit (GNB3/C825T) gene polymorphisms. We determined genetic variants using the TaqMan system in a large cohort representing the general population in Japan (867 males, 1,013 females). Logistic analysis indicated that the ADD1/ G460W polymorphism was associated with hypertension in female subjects. The odds ratio of the WW genotype for hypertension was 1.53 (95%Cl, 1.12-2.08) over the WG+GG genotype (p=0.0070, p corrected (p(c)) =0.0420 corrected by the Bonferroni method). The ADRB1/R389G polymorphism tended to be associated with hypertensive status in male subjects (p=0.0117, p(c)=0.0702). The odds ratio of the GG genotype for hypertension was 0.38 (95%CI, 0.167-0.780) over the RR+RG genotype. The GNB3/C825T polymorphism was not associated with hypertensive status in either male or female subjects. The present results do not agree with those in previous reports. Almost all common variants may have only a modest effect on common diseases, and a single study even employing 1,880 subjects may lack the statistical power to detect a real association. Accordingly, it will be necessary to verify the association between these three genes and hypertension using a larger number of subjects from the Suita cohort or another population.
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PMID:Association between hypertension and the alpha-adducin, beta1-adrenoreceptor, and G-protein beta3 subunit genes in the Japanese population; the Suita study. 1505 53

The response of blood pressure to thiazide diuretics (TZDs) differs among individuals. The prediction of the antihypertensive effect of TZDs is important for realizing individualized therapy in the management of hypertension. The aim of this study was to identify the single nucleotide polymorphisms (SNPs) susceptible to the antihypertensive effect of TZDs, particularly focusing on genes related to water-electrolyte absorption in the kidney. Seventy-six outpatients (mean age, 65.4+/-9.0 years) with essential hypertension (EHT) taking TZDs were retrospectively assessed. We defined as responders (R) those whose mean blood pressure was lowered by more than 5 mmHg after the use of TZDs. Forty-eight SNPs in 17 genes (ADD1, GNB3, TSC [SLC12A3], MLR [NR3C2], NCX1 [SLC8A1], WNK1, WNK4, AGT, ACE, AT1 [AGTR1], CYP11B2, ADRB1, ADRB2, ADRB3, ADRA1A, ADRA1B, ADRA2A) were genotyped in the 76 patients. The SNPs in TSC, MLR, NCX1, WNK1, and WNK4 were identified by direct sequencing and those with minor frequencies of greater than 5% were genotyped in this study. The comparison of polymorphism prevalence between R and non-responders (NR) showed significant differences in TSC C1784T (C allele vs. T allele, odds ratio (OR)=3.81, p =0.016, confidence interval (CI): 1.25-11.63) and ADRB3 T727C (Trp64Arg) (T allele vs. C allele, OR=4.59, p =0.005, CI: 1.54-13.68). The blood pressure (BP) in patients homozygous for the major alleles of both TSC C1784T and ADRB3 T727C were significantly reduced by TZD treatment; however, the BP in those homozygous for the minor allele and heterozygous (TSC C1784T: TT+CT; ADRB3 T727C: CC+CT) for both SNPs were not significantly changed after TZD treatment. Both newly detected TSC C1784T and ADRB3 T727C are gene polymorphisms susceptible to the antihypertensive effect of TZDs in patients with EHT. Thus, the prediction of BP reduction by TZDs may be possible by evaluating these two SNPs.
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PMID:The thiazide-sensitive Na(+)-Cl(-) cotransporter gene, C1784T, and adrenergic receptor-beta3 gene, T727C, may be gene polymorphisms susceptible to the antihypertensive effect of thiazide diuretics. 1582 64

The beta-adrenergic receptors (ADRBs) are cell surface receptors that play central roles in the sympathetic nervous system. Pharmacological targeting of two of these receptors, ADRB1 and ADRB2, represents a widely used therapeutic approach for common and important diseases including asthma, hypertension and heart failure. Genetic variation in both ADRB1 and ADRB2 has been linked to both in vitro and clinical disease phenotypes. More recently, interest has shifted to studies that explore potential interaction between variation in ADRBs and medications directed at these important receptors. This paper reviews the current state of knowledge and understanding of ADRB genetic variation and explores the likely direction of future studies in this area.
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PMID:Pharmacogenetics of the human beta-adrenergic receptors. 1663 83

The association between polymorphisms in the beta1, beta2 and alpha2B adrenergic receptor (ADR) genes (ADRB1, ADRB2 and ADRA2B) and resting heart rate was examined in white and African-American participants of the HyperGEN Study. All analyses were adjusted for age, sex, body mass index, alcohol use, smoking status and daily exercise within strata of race, hypertension status and beta-blocker use. The Ser49Gly polymorphism of the beta1 ADR was associated with resting heart rate in hypertensive African-Americans and hypertensive whites taking beta-blockers, with carriers of the Gly allele having a higher mean resting heart rate by 2.7 and 4.4 beats per minute (bpm), respectively. The Arg389Gly polymorphism of the beta1 ADR was associated with lower heart rate in the normotensive African-American sample. A beta1 haplotype (Ser49Gly-Arg389Gly) was modestly associated with resting heart rate in the hypertensive African-Americans. The alpha2B C/A polymorphism was associated with heart rate in hypertensive whites, and both whites and African-Americans taking beta-blockers, with carriers of the A allele having a higher mean resting heart rate. In summary, each of the ADR gene polymorphisms was associated with heart rate in at least one stratum studied, but there was no consistent association from which one would infer a large genetic contribution to heart rate.
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PMID:Adrenergic receptor polymorphisms associated with resting heart rate: the HyperGEN Study. 1690 3

Hypertension is a complex multifactorial disorder that is thought to result from an interaction between genetic background and environmental factors. Although various loci and genes have been implicated in predisposition to hypertension by genetic linkage analyses and candidate gene association studies, the genes that confer susceptibility to this condition remain to be identified definitively. We examined the relations of nine candidate gene polymorphisms to blood pressure (BP) and the prevalence of hypertension in a population-based study. The 2238 subjects (1110 women, 1128 men) were aged 40 to 79 years and were randomly recruited for a population-based prospective cohort study of aging and age-related diseases in Japan. BP was measured with subjects having rested in a sitting position for at least 15 min. Genotypes for the 160C-->T (Arg54Trp) polymorphism of QPCT, the C-->T (Pro198Leu) polymorphism of GPX1, the 137,346T-->C polymorphism of FYN, the -344C-->T polymorphism of CYP11B2, and the A-->G (Ser49Gly) polymorphism of ADRB1 were determined with a fluorescence-based allele-specific DNA primer assay system; those for the A-->G polymorphism of CNR2, the I/D (22,375delAC) polymorphism of CAV1, and the -1213T-->C polymorphism of ESR2 by melting curve analysis, and that for the (GT)n polymorphism of COL1A2 were determined by DNA fragment analysis. The polymorphism of FYN was associated with systolic and diastolic BP in women. In men, polymorphisms of CNR2, QPCT, GPX1, COL1A2, CYP11B2, and ESR2 were associated with systolic and diastolic BP, those of CAV1 and FYN with systolic BP, and that of ADRB1 with diastolic BP. The polymorphisms of QPCT and CYP11B2 were also associated with the prevalence of hypertension in men. These results suggest that polymorphisms of QPCT and CYP11B2 are determinants of BP and the development of hypertension in Japanese men.
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PMID:Association of gene polymorphisms with blood pressure and the prevalence of hypertension in community-dwelling Japanese individuals. 1733 44

Echocardiographic measures of cardiac target organ damage, including left ventricular mass and relative wall thickness, are powerful predictors of heart disease morbidity and mortality. The aim of this study is to investigate whether single nucleotide polymorphisms in candidate genes for hypertension and heart disease have effects on quantitative measures of hypertensive cardiac target organ damage, independent of their actions on blood pressure levels, in a cohort of hypertensive black sibships. To detect replication of genetic effects across samples, this study took advantage of the affected sibling pair design and created 2 samples, each with 448 unrelated individuals. As part of the Genetic Epidemiology Network of Arteriopathy Study, subjects were screened using 2D echocardiography, and 395 single nucleotide polymorphisms in 80 candidate genes were genotyped. Linear regression was used to test for single nucleotide polymorphisms significantly associated with left ventricular mass index (g/m(2.7)) or relative wall thickness after adjusting for associated covariates. Significant single nucleotide polymorphisms were subsequently tested for consistent directionality in genotype-phenotype relationships across samples. Three single nucleotide polymorphisms, 1 each in the APOE, SCN7A, and SLC20A1 genes, were significantly associated in both samples with left ventricular mass index and had replicate genotype-phenotype relationships. One in the ADRB1 gene was significantly associated with relative wall thickness with replicate effects in both samples. We identified genetic variation that significantly influences left ventricular traits with replicable effects in a cohort of hypertensive, black siblings.
Hypertension 2007 May
PMID:Genetic variations associated with echocardiographic left ventricular traits in hypertensive blacks. 1733 38

Association of polymorphism of b1-adrenoreceptors gene and cytochrome 2D6 gene with efficacy of b-adrenoblocker betaxolol was studied in 81 patients with I and II degree arterial hypertension. Betaxolol (10-20 mg/day) was given for 4 weeks, its efficacy was assessed by office blood pressure (BP) measurements, 24-hour BP and ECG monitoring and standard exercise test. At the end of the study significant lowering of systolic and diastolic BP was noted by 11,8 +/- 2,47 (p=0,001) and 7,8 +/- 1,68 mm Hg (p=0,001), respectively. Heart rate (HR) at rest lowered by 19,8 +/- 1,96 beats/min (p=0,0001). At analysis of individual reaction of patients to treatment with betaxolol it turned out that decrease of BP and HR was variable, but their distribution in the group did not differ significantly from normal. Hypotensive activity and influence on HR were confirmed by results of all instrumental investigations. No significant differences were revealed in dynamics of systolic and diastolic BP both at rest and at effort between patients with different genotypes of polymorphic marker Gly389Arg of ADRB1 gene. Compared with carriers of genotype Ser/Ser carriers of genotype Ser/Pro of polymorphic marker Pro34Ser of Cyp2D6 gene had significantly more pronounced decrease of HR at the background of treatment with betaxolol: - 32,6 +/- 4,77 and - 18,4 +/- 2,01 beats/min (p=0,023) at rest and - 30,1 +/- 3,05 and - 24,0 +/- 2,59 beats/min (p=0,043) at maximal exercise, respectively. These patients had also more pronounced lowering of diastolic BP at maximal work load and more pronounced increase of exercise duration at the background of treatment. Thus efficacy of betaxolol in patients with hypertension was associated solely with genotype of polymorphic marker Ser34Pro of CYP2D6 gene. In patients having in genotype Pro allele of polymorphic marker Pro34Ser of CYP2D6 gene therapy with betaxolol is more effective, than in homozygote carriers of Ser allele. This can be related to low rate of metabolism of the preparation in these patients.
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PMID:[Genetic aspects of individual sensitivity to betaxolol in patients with arterial hypertension]. 1842 52

Numerous studies have demonstrated that beta(1)- and beta(2)-adrenergic receptor gene (ADRB1 and ADRB2) variants influence cardiovascular risk and beta-blocker responses in hypertension and heart failure. We evaluated the relationship between ADRB1 and ADRB2 haplotypes, cardiovascular risk (death, nonfatal myocardial infarction (MI), and nonfatal stroke), and atenolol-based vs. verapamil sustained-release (SR)-based antihypertensive therapy in 5,895 coronary artery disease (CAD) patients. After an average of 2.8 years, death rates were higher in patients carrying the ADRB1 Ser49-Arg389 haplotype (hazard ratio (HR) 3.66, 95% confidence interval (95% CI) 1.68-7.99). This mortality risk was significant in patients randomly assigned to verapamil SR (HR 8.58, 95% CI 2.06-35.8) but not atenolol (HR 2.31, 95% CI 0.82-6.55), suggesting a protective role for the beta-blocker. ADRB2 haplotype associations were divergent within the treatment groups but did not remain significant after adjustment for multiple comparisons. ADRB1 haplotype variation is associated with mortality risk, and beta-blockers may be preferred in subgroups of patients defined by ADRB1 or ADRB2 polymorphisms.
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PMID:beta-adrenergic receptor gene polymorphisms and beta-blocker treatment outcomes in hypertension. 1861 4

The role of nitric oxide (NO)-containing nerves in adrenergic neurotransmission in hypertension was studied in mesenteric resistance arteries without endothelium in 2-kidney-1-clip renal hypertensive rats (2K-1C RHR) and sham-operated normotensive rats (Sham-R). Mesenteric vascular beds isolated from 2K-1C RHR and Sham-R were perfused with Krebs solution and changes in perfusion pressure were measured with a pressure transducer. Perfusion of a NO synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), markedly augmented vasoconstrictor responses to periarterial nerve stimulation (PNS) without affecting vasoconstriction induced by exogenously injected noradrenaline. L-NAME significantly increased the neurogenic release of NA evoked by PNS in both 2K-1C RHR and Sham-R preparations. The facilitatory effect of L-NAME based on the inhibition of NO production in 2K-1C RHR was less than that in Sham-R. These results suggest that the function of NO-containing nerves, which presynaptically inhibit adrenergic neurotransmission, is decreased in the renovascular hypertensive model rat.
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PMID:[Functional alteration of nervous system in renovascular hypertension]. 1918 45

Aim of the study was investigation of association of polymorphic markers Gly389Arg and Ser49Gly of ADRB1 gene, Gly1l6Arg and Glu27Gln of ADRB2 gene, Trp64Arg of ADRB3 gene, and 825 of GNB3 gene with structural and functional peculiarities of the left ventricular (LV) myocardium in patients with hypertensive disease. We examined 177 patients - 83 (46.9%) men and 94 (53.1%) women. Mean age was 60.6 +/- 0.76 years. In the studied group there were 19 patients (10.9%) with I degree arterial hypertension (AH), 57 patients (32.8%) with II degree AH, and 101 patients (56.3%) with III degree AH. Structural peculiarities of LV myocardium were investigated with the help of echocardiography. There turned out to be 40 patients without signs of LV hypertrophy and 137 patients with increase of LV myocardial mass index. patients with LV hypertrophy had higher frequency of genotype Arg/Arg of polymorphic maker Gly398Arg of ADRB1 gene (=0.008. OR 2.32 [CI 1.34 - 4.11]). In patients with concentric and eccentric hypertrophy significantly higher frequency of Arg/Arg genotype compared with patients with normal LV geometry and concentric LV remodeling was also noted. At conduction of multifactorial analysis independently connected with increase of LV myocardial mass turned out age of patients, level of systolic arterial pressure, presence of excessive body mass and carriage of Arg/Arg genotype of polymorphic marker Gly389Arg of ADRB1 gene.
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PMID:[Myocardial hypertrophy in patients with hypertensive disease: the role of genetic polymorphism of beta-adrenoreactive structures]. 2014 52


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