Orthostatic blood pressure dysregulation and polymorphisms of β-adrenergic receptor genes in hypertensive patients.
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ABSTRACT:
SUBMITTER: Gao Y
PROVIDER: S-EPMC8032172 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AimThe genetic background of orthostatic blood pressure dysregulation remains poorly understood. Since the renin-angiotensin system plays an important role in blood pressure regulation and response to position change, we hypothesized that angiotensin-converting enzyme (ACE) and ACE2 genetic polymorphisms might contribute, at least partially, to orthostatic blood pressure dysregulation in hypertensive patients.MethodsTwo tag single nucleotide polymorphisms (SNPs) of ACE2 and ACE I/D were genotyped in 3630 untreated hypertensive patients and 826 normotensive subjects. Orthostatic hypertension was defined as an increase in systolic blood pressure of 20 mmHg or more and orthostatic hypotension as a drop in blood pressure of 20/10 mmHg or more within three minutes of assumption of upright posture.ResultsFemale and male patients had similar rates of orthostatic hypertension (16.5% vs 15.3%) and hypotension (22.5% vs 23.8%). No significant differences were detected in the minor allele frequency of ACE2 rs2106809, rs2285666, or ACE I/D in either female or male patients with orthostatic hypertension (15.1%, 22.7%, 19.6%, respectively), hypotension (13.8%, 25%, 16.5%), or normal orthostatic blood pressure response (14.4%, 21.9%, 15.8%) in additive, dominant or recessive models after adjustment for confounders (all P>0.05). The orthostatic changes in systolic and diastolic blood pressure were also comparable among patients carrying different genotypes. Similar results were observed in normotensive subjects.ConclusionThese data provide no support for the involvement of ACE or ACE2 in the genetic predisposition to orthostatic hypotension or hypertension.
| S-EPMC4007186 | biostudies-literature
Project description:Beta-adrenergic receptors (beta-ARs) play a pivotal role in the cardiovascular regulation. In the human heart beta1- and beta2-ARs dominate in atria as well as in ventricle influencing heart rate and myocardial contractility. Some single nucleotide polymorphisms (SNPs) of beta-ARs might influence cardiovascular function. However, the influence of beta-AR genes SNPs on hemodynamic parameters at rest and their reactivity under stress is still not well known. We aimed to explore the associations between four selected beta-ARs gene polymorphisms and selected cardiovascular measures in eighty-seven young healthy subjects. While in beta1-AR polymorphism rs1801252 no significant association was observed, second beta1-AR polymorphism rs1801253 was associated with decreased cardiac output and cardiac index during all phases and with decreased flow time corrected and ejection time index at rest and during mental arithmetics. Polymorphism rs1042713 in beta2-AR was associated with alterations in blood pressure variability at rest and during head-up-tilt, while rs1042714 was associated predominantly with decreased parameters of cardiac contractility at rest and during mental arithmetics. We conclude that complex analysis of various cardiovascular characteristics related to the strength of cardiac contraction and blood pressure variability can reveal subtle differences in cardiovascular sympathetic nervous control associated with beta-ARs polymorphisms.
| S-EPMC8884389 | biostudies-literature
Project description:Background Orthostatic blood pressure dysregulation, including orthostatic hypotension (OH) and orthostatic hypertension (OHT), is common in the elderly. The association between OH and, to a lesser extent, OHT with geriatric syndromes is controversial and little investigated. Our objective was to assess the association between orthostatic blood pressure dysregulation and geriatric syndromes in an ambulatory outpatient population. Methods This observational study included all outpatients for whom a one-visit comprehensive geriatric assessment was performed during a year. OH was defined as a decrease of at least 20 mmHg in systolic blood pressure (SBP) and/or 10 mmHg in diastolic blood pressure (DBP) after 1 or 3 min of standing. OHT was defined as an increase of more than 20 mmHg in SBP after 1 or 3 min of standing. Comorbidities, drugs regimen, a history of previous falls, nutritional, frailty, functional and cognitive status were compared between patients with OHT or OH and controls (NOR). Results Five hundred thirty patients (mean age: 82.9 ± 5.1 years) were included. 19.6% had an OH and 22.3% an OHT. OHT patients were more frequently female, had more diabetes and a lower resting SBP than patients with NOR. OH patients had a higher resting SBP than NOR. After adjusting for age, sex, resting SBP and diabetes, OHT was associated with a low walking speed (OR = 1.332[1.009–1.758]; p = 0.043) and severe cognitive impairment at MMSe score (OR = 1.629[1.070–1.956]; p = 0.016) compared to NOR. Conversely, OH was associated with a lower grip strength (p = 0.016) than NOR. Conclusion OHT and OH are common in elderly but associated with different geriatric phenotypes. Supplementary Information The online version contains supplementary material available at 10.1186/s12877-022-02844-8.
| S-EPMC8881862 | biostudies-literature
Project description:In Parkinson's disease (PD), cardiovascular dysautonomia accumulates with disease progression, but studies are lacking on the natural history behind each subtype except orthostatic hypotension. This study investigated the early natural history of orthostatic blood pressure (BP) subtypes in PD. Two hundred sixty-seven early PD patients were included. Their cardiovascular functions were assessed by head-up tilt-test and 123I-metaiodobenzylguanidine scintigraphy. All patients were classified as having supine hypertension (SH), orthostatic hypertension (OHT), delayed orthostatic hypotension (dOH), or orthostatic hypotension (OH) according to consensus criteria. The patients were assigned to one of three groups: extreme BP dysregulation (BPextreme), mild BP dysregulation (BPmild), and no BP dysregulation (BPnone) according to their orthostatic BP subtypes. The autonomic functions of 237 patients were re-assessed after approximately 3 years. Among initially enrolled subjects, 61.8% of the patients showed orthostatic BP dysregulation: 29.6% in the BPextreme group and 32.2% in the BPmild group. At follow-up, the BPextreme group increased in number, while the BPmild group diminished. Two-thirds of the initial BPextreme patients maintained their initial subtype at follow-up. In comparison, 40.7% of the initial BPmild patients progressed to the BPextreme group, and 32.4% and 14.7% of the initial BPnone group progressed to BPextreme and BPmild groups, respectively. Cardiac denervation was most severe in the BPextreme group, and a linear gradient of impairment was observed across the subtypes. In conclusion, various forms of positional BP dysregulation were observed during the early disease stage. SH and OH increased with disease progression, while OHT and dOH decreased, converting primarily to SH and/or OH.
| S-EPMC10284855 | biostudies-literature
Project description:Variation in the beta-1 and beta-2 adrenergic receptor genes (ADRB1 and ADRB2, respectively) may influence cardiovascular reactivity including orthostatic stress. We tested this hypothesis in a head-up tilt (HUT) screening protocol in healthy young adults without history of syncope. Following brachial arterial catheter insertion, 120 subjects (age 18-40, 72 females, Caucasian) underwent 5min 60° HUT. Polymorphisms tested were: Ser49/Gly and Arg389/Gly in ADRB1; and Arg16/Gly, Gln27/Glu, and Thr164/Ile in ADRB2. Three statistical models (recessive, dominant, additive) were evaluated using general linear models with analysis for each physiologic variable. A recessive model demonstrated a significant association between Arg16/Gly and: absolute supine and upright HR; HUT-induced change in cardiac index (CI), stroke index (SI) and systemic vascular resistance (SVR); and supine and upright norepinephrine values. Blood pressure was not influenced by genotype. Fewer associations were present for other polymorphisms: Ser49/Gly and the change in SI (dominant model), and Arg389/Gly and supine and HUT norepinephrine (additive model). We conclude that in this population, there is a robust association between Arg16/Gly and HUT responses, such that 2 copies of Arg16 increase supine and upright HR, and greater HUT-induced decreases in CI and SI, with greater increases in SVR and norepinephrine. ADRB1 gene variation appears to impact SI and plasma NE levels but not HR. Whether ADRB2 gene variation is ultimately disease-causing or disease-modifying, this study suggests an association between Arg16/Gly and postural hemodynamics, with sympathetic noradrenergic activity affected in a similar direction. This may have implications in the development of orthostatic disorders.
| S-EPMC3167015 | biostudies-literature
Project description:RationaleSeveral studies suggest that patients with asthma who are homozygous for arginine at the 16th position of the beta2-adrenergic receptor may not benefit from short-acting beta-agonists.ObjectivesWe investigated whether such genotype-specific effects occur when patients are treated with long-acting beta-agonists and whether such effects are modified by concurrent inhaled corticosteroid (ICS) use.MethodsWe compared salmeterol response in patients with asthma homozygous for arginine at B16 (B16Arg/Arg) with those homozygous for glycine at B16 (B16Gly/Gly) in two separate cohorts. In the first, subjects were randomized to regular therapy with salmeterol while simultaneously discontinuing ICS therapy. In the second, subjects were randomized to regular therapy with salmeterol while continuing concomitant ICS.ResultsIn both trials, B16Arg/Arg subjects did not benefit compared with B16Gly/Gly subjects after salmeterol was initiated. In the first cohort, compared with placebo, the addition of salmeterol was associated with a 51.4 L/min lower A.M. peak expiratory flow (PEF; p = 0.005) in B16Arg/Arg subjects(salmeterol, n = 12; placebo, n = 5) as compared with B16Gly/Gly subjects (salmeterol, n = 13; placebo, n = 13). In the second cohort, B16Arg/Arg subjects treated with salmeterol and ICS concurrently (n = 8) had a lower A.M. PEF (36.8 L/min difference, p = 0.048) than B16Gly/Gly subjects (n = 22) treated with the same regimen. In addition, B16 Arg/Arg subjects in the second cohort had lower FEV1 (0.42 L, p = 0.003), increased symptom scores (0.2 units, p = 0.034), and increased albuterol rescue use (0.95 puffs/d, p = 0.004) compared with B16Gly/Gly subjects.ConclusionsRelative to B16Gly/Gly patients with asthma, B16Arg/Arg patients with asthma may have an impaired therapeutic response to salmeterol in either the absence or presence of concurrent ICS use. Investigation of alternate treatment strategies may benefit this group.
| S-EPMC2662935 | biostudies-literature
Project description:Nondipping nocturnal blood pressure (BP) is associated with target organ damage and cardiovascular disease. We hypothesized that ?1- and ?2-AR-associated single nucleotide polymorphisms (SNPs) would associate with nondipping BP patterns. Participants (n = 497, age range 30-74 years, 40% female) of the Wisconsin Sleep Cohort Study with at least one ambulatory BP monitoring test were included. Nondipping was defined as less than a 10% dip in sleep BP compared with wake BP. Dipping ratios were calculated as sleep/wake BP. Single nucleotide polymorphisms in the ?1-AR (rs7076938, tagging for Gly389Arg) and ?2-AR (rs17778257 and rs2400707, tagging for Arg16Gly and Gln27Glu) were selected. ?2-AR SNP rs2400707 A-positive subjects (tagging for Glu27) had higher systolic and diastolic dipping ratios in a dose-response fashion. Systolic dipping ratios were: GG = 0.846; AG = 0.854; AA = 0.861 (P = .015). Diastolic dip ratios were: GG = 0.807; AG = 0.815; AA = 0.824 (P = .026). The ?2-AR rs17778257/rs2400707 A/A haplotype was associated with dipping ratios and systolic nondipping status (nondipping odds radio 2.0 [1.0-3.8] for A/A versus A/G). Results were similar when models included participants on antihypertensive medications. Higher dipping ratios indicating a lack of nocturnal BP dipping are associated with ?2-AR polymorphisms. Nocturnal dipping patterns may be modulated by ?2-AR polymorphisms.
| S-EPMC3071556 | biostudies-literature
Project description:BackgroundPulmonary edema and associated impaired oxygenation are a major reason for rejection of donor lung allografts offered for transplantation. Clearance of pulmonary edema can be upregulated by stimulation of β-adrenergic receptors (βARs). Single-nucleotide polymorphisms (SNPs) in βAR genes have functional effects in vitro and in vivo. We hypothesized that SNPs in βAR genes would be associated with rates of utilization of donor lung allografts offered for transplantation.MethodsNine hundred fifty-one organ donors were genotyped for 4 amino-acid-coding SNPs in the βAR genes. Lung allograft utilization was compared among donors stratified by genotypes.ResultsUtilization of donor lung allografts was 55% vs 35% (p = 0.02) among donors with GG vs AA/AG genotypes of the Ser49Gly SNP, 39% vs 32% (p = 0.04) with GG vs AA/AG genotype of Gly16Arg SNP and 37% vs 32% (p = 0.1) with CC vs GC/GG genotype of the Arg389Gly SNP. In the combined analysis, donors carrying 0 or 1 associated genotype had a utilization rate of 33%, whereas donors carrying 2 or 3 associated genotypes had utilization rates of 44% and 58%, respectively (p = 0.008). There was a stepwise decrease in chest radiograph infiltrates and an increase in partial pressure of oxygen/fraction of inspired oxygen (PaO(2)/FIO(2)) with an increasing number of these associated genotypes.ConclusionGenetic variants in the βAR genes among organ donors are associated with higher rates of lung allograft utilization. The increased utilization may be related to increased clearance of pulmonary edema and improved oxygenation in donors with favorable genotypes and suggests that βAR agonists may have a role in donor management.
| S-EPMC3019270 | biostudies-literature
Project description: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.
| S-EPMC2675574 | biostudies-literature
Project description:BackgroundActivation of beta-1 adrenoreceptor (β1-AR) in the kidney releases renin that plays a major role in the maintenance of blood pressure. Genetic variation in β1-AR could therefore alter the physiological and clinical effects of this hormone. We tested this hypothesis in patients from a primary care cohort being screened for primary hyperaldosteronism (n = 467).MethodsDemographic and hemodynamic data were measured and plasma renin was determined by a standard immunoassay. Subjects were genotyped for the 2 common single-nucleotide polymorphisms Arg389Gly (rs1801253) and Ser49Gly (rs1801252), and thus the 4 possible haplotypes in β1-AR gene.ResultsIn patients being screened for hyperaldosteronism, plasma renin was significantly elevated in Ser49 homozygotes (49SS) compared with Gly49 (49G) allele carriers (0.307 ± 0.03 vs. 0.164 ± 0.05; P = 0.01). However, this did not translate into differences in either blood pressure or heart rate. On the other hand, the Arg389Gly polymorphism did not affect either plasma renin or blood pressure in this group. There was also no evidence that the 2 loci were linked in this group of patients.ConclusionThese data suggest that in this cohort the Ser49 variant of the Ser49Gly β1-AR gene polymorphism associates with higher renin levels. However, these common β1-AR gene polymorphisms do not affect blood pressure in the same cohort.
| S-EPMC6475877 | biostudies-literature