title: G-protein-coupled receptor kinase 4 polymorphisms predict blood pressure response to dietary modification in Black patients with mild-to-moderate hypertension.
abstract: Dopamine via G-protein-coupled receptor kinase 4 (GRK-4) regulates sodium (Na) balance in the proximal tubule of the kidney. Single-nucleotide polymorphisms of GRK-4 have been linked to impaired natriuresis and salt-sensitive hypertension. The purpose of this report was to determine the effect of GRK-4 gene polymorphisms on the blood pressure (BP) responses to dietary intervention. Black subjects aged 50-75 years with mild-to-moderate hypertension were randomised to an 8-week dietary intervention (n=40) or standard diet (n=40). BP was measured at baseline and at 8 weeks using 24-h ambulatory BP. All subjects underwent DNA analysis for the R65L and A142V polymorphisms. Data were analysed using generalised linear models. For the whole group, between-diet differences in mean 24-h ambulatory systolic BP was -4.53 mm Hg (95% confidence interval -9.05 to -0.01, P=0.05). In the intervention arm, the combined CC and CT group of the A142V showed a significant reduction in both systolic and diastolic ambulatory BP (-10 mm Hg, P=0.023 and -6.5 mm Hg, P=0.01, respectively), whereas the TT group demonstrated no reduction. Similarly, the combined GG and GT groups of the R65L showed a significant reduction in ambulatory BP (-10.6 mm Hg for systolic, P=0.004 and 5.8 mm Hg for diastolic, P=0.006). There was no response in the TT group. GRK-4 polymorphisms predict BP response to dietary modification in Black subjects with mild-to-moderate hypertension. These data may provide at least one among a range of clinical tools to target selected hypertensives to dietary intervention.
authors.affiliation: Division of Nephrology and Hypertension, E13 Groote Schuur Hospital, Observatory, Cape Town, South Africa. brian.rayner@uct.ac.za
authors.forename: B
authors.initials: B
authors.lastname: Rayner
authors.forename: R
authors.initials: R
authors.lastname: Ramesar
authors.forename: K
authors.initials: K
authors.lastname: Steyn
authors.forename: N
authors.initials: N
authors.lastname: Levitt
authors.forename: C
authors.initials: C
authors.lastname: Lombard
authors.forename: K
authors.initials: K
authors.lastname: Charlton
mesh_terms: D000368:Aged; D044383:Black People / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D018660:Blood Pressure Monitoring, Ambulatory; D005260:Female; D054771:G-Protein-Coupled Receptor Kinase 4 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000178:diet therapy* / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D013019:South Africa / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D054771:G-Protein-Coupled Receptor Kinase 4; C517855:GRK4 protein, human