Association of G-protein-coupled receptor kinase 4 haplotypes, but not HSD3B1 or PTP1B polymorphisms, with essential hypertension

  title={Association of G-protein-coupled receptor kinase 4 haplotypes, but not HSD3B1 or PTP1B polymorphisms, with essential hypertension},
  author={Helen Speirs and K Katyk and Natasha N. Kumar and Adam V. Benjafield and William YS Wang and Brian J. Morris},
  journal={Journal of Hypertension},
Objective: To perform association studies of polymorphisms of the potential candidate essential hypertension (HT) genes GRK4, PTP1B and HSD3B1. Methods: Subjects consisted of 168 unrelated, Caucasian essential hypertensive (HT) patients and 312 normotensive (NT) controls. Biological power was increased by ensuring subjects in each group had parents with the same blood pressure (BP) status as theirs. Three GRK4γ variants (R65L, A142V and A486V), one HSD3B1 variant (T←C Leu338) and one PTP1B… 
G protein receptor kinase 4 polymorphisms: &bgr;-Blocker Pharmacogenetics and treatment-related outcomes in Hypertension
The results suggest that the presence of GRK4 variant alleles may be important determinants of blood pressure response to atenolol and risk for adverse cardiovascular events.
G protein-coupled receptor kinases (GRKs) are important regulatory proteins for many G proteincoupled receptors, but little is known about GRK4 pharmacogenetics. We hypothesized three nonsynonymous
G protein-coupled receptor kinase 4 gene variants are not associated with preeclampsia in Northern Han Chinese
The GRK4 polymorphisms do not seem to have an important role in PE in this population of Northern Han Chinese, and there was also no relationship with the severity of PE.
Common variants of the G protein-coupled receptor type 4 are associated with human essential hypertension and predict the blood pressure response to angiotensin receptor blockade
Two studies showed for the first time the association between GRK4142V and a larger decrease in BP with ARBs in hypertensive patients.
G-protein-coupled receptor kinase 4 polymorphisms and blood pressure response to metoprolol among African Americans: sex-specificity and interactions.
Results suggest a sex-specific relationship between GRK4 A142V and blood pressure response among African-American men with early hypertensive nephrosclerosis.
Association of HSD3B1 and HSD3B2 gene polymorphisms with essential hypertension, aldosterone level, and left ventricular structure.
BACKGROUND HSD3B1 and HSD3B2 are crucial enzymes for the synthesis of hormonal steroids, including aldosterone. Therefore, HSD3B gene variations could possibly influence blood pressure (BP) by
Variants in Genes Involved in Functional Pathways Associated with Hypertension in African Americans
Results show very modest effects and do not fully replicate previous studies, but if variants in the G‐protein coupled receptor Kinase‐4, nitric oxide synthase‐3, or angiotensin converting enzyme (ACE) genes are associated singly or through complex interactions, with HBP in African Americans aged 18–49 years is determined.
Association Study of G Protein‐Coupled Receptor Kinase 4 Gene Variants with Essential Hypertension in Northern Han Chinese
A total of 6 haplotypes were observed in the entire population, with the haplotypes L‐V‐A and R‐A‐A being found to be significantly related to hypertension (P= 0.001), and the A486 allele showed a significant association with HT.
Expression and gene variation studies deny association of human HSD3B1 gene with aldosterone production or blood pressure.
No evidence is found to support confirmation that HSD3B1 is involved in aldosterone synthesis in the human adrenal cortex or that genetic variation in HSD2B1 affects blood pressure or hypertension, favoring the hypothesis that all adrenocortical steroidogenesis is primarily dependent on the type II 3β-hydroxysteroid dehydrogenase.


Haplotype analysis of aldosterone synthase gene (CYP11B2) polymorphisms shows association with essential hypertension
The T−344C and A6547G, but not the T4986C, variants of the aldosterone synthase gene are associated with HT in females of the Anglo-Celtic population studied.
G-protein beta3 subunit gene (GNB3) variant in causation of essential hypertension.
A role for a genetically determined, physiologically active splice variant of the G protein beta3 subunit gene in the causation of essential hypertension is supported.
Association of EDNRA, but not WNK4 or FKBP1B, polymorphisms with essential hypertension
Possible involvement of EDNRA in essential HT is suggested, which transduces most of the vasoconstrictive properties of endothelin‐1, protein kinase lysine deficient 4 (WNK4) whose gene resides in a HT linkage region on chromosome 17, and FK506‐binding protein 1B (FKBP1B), which can reduce blood pressure by increasing nitric oxide.
Association of angiotensin II type 1 receptor gene polymorphism with essential hypertension
The present results implicate the AT1R gene, or a locus in linkage disequilibrium with the variant tested, in the causation of essential HT.
A variation in 3' UTR of hPTP1B increases specific gene expression and associates with insulin resistance.
The data indicate that the 1484insG allele causes PTP1B overexpression and plays a role in insulin resistance, and individuals carrying the 14 84insG variant might particularly benefit from PTP 1B inhibitors, a promising new tool for treatment of insulin resistance.
G protein-coupled receptor kinase 4 gene variants in human essential hypertension
  • R. Felder, H. Sanada, P. Jose
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 2002
Findings provide a mechanism for the D1 receptor coupling defect in the kidney and may explain the inability of the kidney to properly excrete sodium in genetic hypertension.
Association of the α-Adducin Locus With Essential Hypertension
Data suggest that a polymorphism within the α-adducin gene may affect blood pressure in humans.
Genotyping of essential hypertension single-nucleotide polymorphisms by a homogeneous PCR method with universal energy transfer primers.
A simple and homogeneous fluorescent protocol has been developed that has been used to determine the SNP genotype for six loci in a population of hypertensive and normotensive persons and observed a significant association between one SNP and an Italian population of mildly hypertensive patients.
Association of the alpha-adducin locus with essential hypertension.
The data suggest that a polymorphism within the alpha-adducin gene may affect blood pressure in humans, and this work is the first to suggest that this gene may be involved in cellular signal transduction in humans.