G Protein–Coupled Receptor Kinases: Crucial Regulators of Blood Pressure

Yang, Jian; Villar, Van Anthony M.; Armando, Inés; José, Pedro A.; Zeng, Chunyu

doi:10.1161/jaha.116.003519

Cited by 26 publications

(19 citation statements)

References 119 publications

(406 reference statements)

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“…According to previous research, GPR62 is a protein‐encoding gene in humans, and GPR62 is related to pathways of the family of G protein–coupled receptors (GPCRs). Numerous research studies have identified associations between GPCRs and hypertensive disorders (Brinks & Eckhart, ; Harris, Cohn, Pesant, & Eckhart, ; Rockman, Koch, & Lefkowitz, ; X. Wang, Bosonea, Odenbach, & Fernandez‐Patron, ), with abnormal GPCR function leading to increased blood pressure (Yang, Villar, Armando, Jose, & Zeng, ).…”

Section: Resultsmentioning

confidence: 99%

General retrospective mega‐analysis framework for rare variant association tests

Chien

Chiu

2018

Genetic Epidemiology

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Here, we describe a retrospective mega-analysis framework for gene- or region-based multimarker rare variant association tests. Our proposed mega-analysis association tests allow investigators to combine longitudinal and cross-sectional family- and/or population-based studies. This framework can be applied to a continuous, categorical, or survival trait. In addition to autosomal variants, the tests can be applied to conduct mega-analyses on X-chromosome variants. Tests were built on study-specific region- or gene-level quasiscore statistics and, therefore, do not require estimates of effects of individual rare variants. We used the generalized estimating equation approach to account for complex multiple correlation structures between family members, repeated measurements, and genetic markers. While accounting for multilevel correlations and heterogeneity across studies, the test statistics were computationally efficient and feasible for large-scale sequencing studies. The retrospective aspect of association tests helps alleviate bias due to phenotype-related sampling and type I errors due to misspecification of phenotypic distribution. We evaluated our developed mega-analysis methods through comprehensive simulations with varying sample sizes, covariates, population stratification structures, and study designs across multiple studies. To illustrate application of the proposed framework, we conducted a mega-association analysis combining a longitudinal family study and a cross-sectional case-control study from Genetic Analysis Workshop 19.

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Section: Resultsmentioning

confidence: 99%

General retrospective mega‐analysis framework for rare variant association tests

Chien

Chiu

2018

Genetic Epidemiology

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“…Growing evidence support the association between the allelic variants of GRK4 , salt sensitivity, hypertension, and response to antihypertensive drugs [101••]. This has been reviewed by Rayner and Ramesar and Yang et al [64,146]. A recent metaanalysis showed that GRK4 and DRD1 gene polymorphisms, rs1024323 GRK4 (OR = 1.826) and rs4532 of DRD1 genes (OR = 1.833), are associated with hypertension in Caucasians and East Asians, respectively [59].…”

Section: Pathogenesis Of Primary Pediatric Hypertensionmentioning

confidence: 99%

“…Mice harboring GRK4 gene variants such as GRK4 γ 486V are hypertensive on a high-salt diet, while mice harboring GRK4 γ 142V variants are hypertensive on a normal salt diet but not affected by a high-salt diet [149••]. These variants with increased constitutive GRK4 activity have been shown to down-regulate the renal dopaminergic system and upregulate RAAS (AT 1 R) by decreasing and increasing their expression and activities, respectively, in humans [146]. Furthermore, these variants offer new pharmacogenomic approaches in the treatment of hypertension as evidenced by the African-American Study of Kidney Disease (AASK) where GRK4 65L and GRK4 142V predict a reduced response to α-adrenergic blockers [149••].…”

Section: Pathogenesis Of Primary Pediatric Hypertensionmentioning

confidence: 99%

Primary Pediatric Hypertension: Current Understanding and Emerging Concepts

et al. 2017

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The rising prevalence of primary pediatric hypertension and its tracking into adult hypertension point to the importance of determining its pathogenesis to gain insights into its current and emerging management. Considering that the intricate control of BP is governed by a myriad of anatomical, molecular biological, biochemical, and physiological systems, multiple genes are likely to influence an individual's BP and susceptibility to develop hypertension. The long-term regulation of BP rests on renal and non-renal mechanisms. One renal mechanism relates to sodium transport. The impaired renal sodium handling in primary hypertension and salt sensitivity may be caused by aberrant counter-regulatory natriuretic and anti-natriuretic pathways. The sympathetic nervous and renin-angiotensin-aldosterone systems are examples of antinatriuretic pathways. An important counter-regulatory natriuretic pathway is afforded by the renal autocrine/paracrine dopamine system, aberrations of which are involved in the pathogenesis of hypertension, including that associated with obesity. We present updates on the complex interactions of these two systems with dietary salt intake in relation to obesity, insulin resistance, inflammation, and oxidative stress. We review how insults during pregnancy such as maternal and paternal malnutrition, glucocorticoid exposure, infection, placental insufficiency, and treatments during the neonatal period have long-lasting effects in the regulation of renal function and BP. Moreover, these effects have sex differences. There is a need for early diagnosis, frequent monitoring, and timely management due to increasing evidence of premature target organ damage. Large controlled studies are needed to evaluate the long-term consequences of the treatment of elevated BP during childhood, especially to establish the validity of the current definition and treatment of pediatric hypertension.

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“…More details on the sequence-based analyses that led to these phylogenetic divisions are further discussed in the section titled “Phylogenetic classification/structure” in this review. GPCR have been implicated in numerous biological processes such as cognitive responses [6], cardiovascular functions [7], and cancer growth and development [8]. GPCR implication in human disease is reflected by the estimated 50% of pharmaceutical drugs that interact with these receptors [9].…”

Section: Introductionmentioning

confidence: 99%

G protein-coupled receptors: the evolution of structural insight

Gacasan¹,

Baker²,

Parrill

2017

AIMS Biophysics

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G protein-coupled receptors (GPCR) comprise a diverse superfamily of over 800 proteins that have gained relevance as biological targets for pharmaceutical drug design. Although these receptors have been investigated for decades, three-dimensional structures of GPCR have only recently become available. In this review, we focus on the technological advancements that have facilitated efforts to gain insights into GPCR structure. Progress in these efforts began with the initial crystal structure determination of rhodopsin (PDB: 1F88) in 2000 and has continued to the most recently published structure of the A1AR (PDB: 5UEN) in 2017. Numerous experimental developments over the past two decades have opened the door for widespread GPCR structural characterization. These efforts have resulted in the determination of three-dimensional structures for over 40 individual GPCR family members. Herein we present a comprehensive list and comparative analysis of over 180 individual GPCR structures. This includes a summary of different GPCR functional states crystallized with agonists, dual agonists, partial agonists, inverse agonists, antagonists, and allosteric modulators.

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G Protein–Coupled Receptor Kinases: Crucial Regulators of Blood Pressure

Cited by 26 publications

References 119 publications

General retrospective mega‐analysis framework for rare variant association tests

General retrospective mega‐analysis framework for rare variant association tests

Primary Pediatric Hypertension: Current Understanding and Emerging Concepts

G protein-coupled receptors: the evolution of structural insight

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