title: Association of G-protein-coupled receptor kinase 4 haplotypes, but not HSD3B1 or PTP1B polymorphisms, with essential hypertension.
abstract: 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 GRK4gamma variants (R65L, A142V and A486V), one HSD3B1 variant (T<---C Leu) and one PTP1B variant (1484insG) were genotyped by polymerase chain reaction and restriction enzyme digestion or by homogenous MassEXTEND Assay.
  
  
  RESULTS
  The V allele of the A486V variant of GRK4gamma, but not the R65L or A142V variants, showed an association with HT (P = 0.02). The V allele was also associated with an elevation in systolic blood pressure (SBP) (P = 0.002). Although the L65 and the V142 alleles tracked with elevation in diastolic (DBP), this was seen only in male HTs (P = 0.009; P = 0.002, respectively). Haplotype frequencies differed between the HT and NT groups, particularly for the R, V, V haplotype combination of R65L, A142V and A486V, respectively. Neither of the HSD3B1 or PTP1B variants were associated with HT.
  
  
  CONCLUSIONS
  Genetic variation in GRK4gamma was associated with HT in the subjects studied.
authors.affiliation: Basic & Clinical Genomics Laboratory, School of Medical Sciences and Institute for Biomedical Research, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Helen J L
authors.initials: HJ
authors.lastname: Speirs
authors.forename: Ksenia
authors.initials: K
authors.lastname: Katyk
authors.forename: Natasha N
authors.initials: NN
authors.lastname: Kumar
authors.forename: Adam V
authors.initials: AV
authors.lastname: Benjafield
authors.forename: William Y S
authors.initials: WY
authors.lastname: Wang
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Morris
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D000328:Adult; D000368:Aged; D005260:Female; D054771:G-Protein-Coupled Receptor Kinase 4; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*
chemical_list: D015096:3-Hydroxysteroid Dehydrogenases; D017346:Protein Serine-Threonine Kinases; D054771:G-Protein-Coupled Receptor Kinase 4; C517855:GRK4 protein, human; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases