Genetic polymorphisms of the β-adrenergic system: association with essential hypertension and response to β-blockade

Filigheddu, Fabiana; Reid, J E; Troffa, Chiara; Pinna-Parpaglia, Paolo; Argiolas, Giuseppe; Testa, Alessandra; Mh, Skolnick; Glorioso, Nicola

doi:10.1038/sj.tpj.6500247

Cited by 57 publications

(49 citation statements)

References 44 publications

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“…While some groups reported enhanced β-blocker responses in homozygous carriers of the gain-of-function 389R allele in small studies (metoprolol: Liu et al 2003;Johnson et al 2003;atenolol: Sofowora et al 2003), others did not observe effects of the G389R and the S49G polymorphisms in the β1 adrenoceptor gene on β-blocker responses (Filigheddu et al 2004;Karlsson et al 2004;O'Shaughnessy et al 2000). A recent study reported 9% decreases in mean blood pressures for homozygous hypertensives with the 49S389R haplotypes, while blood pressure decreases were virtually absent in homozygous carriers of the 49S389G haplotypes or in 49S389G/ 49G389G diplotypes .…”

Section: Pharmacogeneticsmentioning

confidence: 98%

“…Mixed results were also obtained for the T393C polymorphism in the Gα S gene, the next step in signal transduction of the β1 adrenoceptor. While Jia et al (1999) documented that the T-allele that was associated with enhanced blood pressure, predicted a poor response to β-blocker, others refuted this association (Filigheddu et al 2004). Blood pressurelowering responses of Atenolol in 221 hypertensive individuals were significantly enhanced in homozygote carriers of the GNB3 C allele.…”

Section: Pharmacogeneticsmentioning

confidence: 99%

“…Blood pressurelowering responses of Atenolol in 221 hypertensive individuals were significantly enhanced in homozygote carriers of the GNB3 C allele. One interpretation is that under conditions of increased signalling (in case of the GNB3 T-allele) higher doses of a β-blocker could be necessary to achieve a comparable blood pressure response (Filigheddu et al 2004). On the other hand, Turner et al documented significantly greater decreases in systolic and diastolic blood pressure after a 4-week treatment period with hydrochlorothiazide for carriers of the GNB3 T-allele (Turner et al 2001a,b), an astonishing result, since heterotrimeric G proteins do not contribute to early effects of diuretics.…”

Section: Pharmacogeneticsmentioning

confidence: 99%

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Genetics of arterial hypertension and hypotension

Rosskopf

Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

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Human hypertension affects affects more than 20% of the adult population in industrialized countries, and it is implicated in millions of deaths worldwide each year from stroke, heart failure and ischemic heart disease. Available evidence suggests a major genetic impact on blood pressure regulation. Studies in monogenic hypertension revealed that renal salt and volume regulation systems are predominantly involved in the genesis of these disorders. Mutations here affect the synthesis of mineralocorticoids, the function of the mineralocorticoid receptor, epithelial sodium channels and their regulation by a new class of kinases, termed WNK kinases. It has been learned from monogenic hypotension that almost all ion transporters involved in the renal uptake of Na + have a major impact on blood pressure regulation. For essential hypertension as a complex disease, many candidate genes have been analysed. These include components of the reninangiotensin-aldosterone system, adducin, β-adrenoceptors, G protein subunits, regulators of G protein signalling (RGS) proteins, Rho kinases and G protein receptor kinases. At present, the individual impact of common polymorphisms in these genes on the observed blood pressure variation, on risk for stroke and as predictors of antihypertensive responses remains small and clinically irrelevant. Nevertheless, these studies have greatly augmented our knowledge on the regulation of renal functions, cellular signal transduction and the integration of both. Together, this provides the basis for the identification of novel drug targets and, hopefully, innovative antihypertensive drugs.

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Section: Pharmacogeneticsmentioning

confidence: 98%

Section: Pharmacogeneticsmentioning

confidence: 99%

Section: Pharmacogeneticsmentioning

confidence: 99%

See 1 more Smart Citation

Genetics of arterial hypertension and hypotension

Rosskopf

Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

View full text Add to dashboard Cite

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“…[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]27,28 Of the 19 eligible articles, the study of Gu et al 28 was replaced by their earlier report, 10 as these two articles reported the same data. Wu et al 5 provided data on two Chinese minorities, the Hani and Yi, residents of the remote rural area of Yunnan, China.…”

Section: Selection Of Studiesmentioning

confidence: 99%

“…Similar results were found in the comparison between the C79 and G79 alleles. 3 In clinical and epidemiologic populations, some studies have indicated that the A46G polymorphism [4][5][6][7][8][9][10] as well as the C79G polymorphism 5,6,8,10,11 in the ADRB2 gene is associated with essential hypertension (or BP level). Other studies have been unable to replicate these findings.…”

Section: Introductionmentioning

confidence: 99%

A46G and C79G polymorphisms in the β2-adrenergic receptor gene (ADRB2) and essential hypertension risk: a meta-analysis

et al. 2010

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No consensus has been reached on the association between the b2-adrenergic receptor polymorphisms A46G and C79G and essential hypertension risk. We performed a meta-analysis to confirm the possible association. After reviewing 303 reports in PubMed and 359 reports in Embase, we included in our meta-analysis 18 articles (20 studies) that met our inclusion criteria. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. There was no statistical association between A46G and hypertension risk in all subjects, Asians or Caucasians. However, an association was observed in the dominant genetic model (AA vs. (AG+GG)) (P¼0.04, odds ratio (OR)¼1.38, 95% confidence interval (CI) 1.01-1.87, P heterogeneity ¼0.98, fixed-effects model) in the subgroup of mixed Africans. No overall statistical association could be found between C79G and hypertension risk or any ethnic subgroup. In the research conducted on severe hypertension (systolic blood pressure X160 mm Hg and/or diastolic blood pressure X95 mm Hg hypertensive population), significant association was found in the dominant genetic model (CC vs. (CG+GG)) (P¼0.04, OR¼1.38, 95% CI 1.02-1.86, P heterogeneity ¼0.03, random-effects model), and there was also a borderline significance between the C79 allele and severe hypertension (P¼0.05, OR¼1.26, 95% CI 1.00-1.57, P heterogeneity ¼0.04, random-effects model). No association could be found in this study between the two polymorphisms and stage 2 hypertension. More studies stratified for different ethnicities and different stages of hypertension should be performed in the future.

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