G-protein-coupled receptor kinase 4 polymorphisms predict blood pressure response to dietary modification in Black patients with mild-to-moderate hypertension

摘要

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 (n40) or standard diet (n40). 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, P0.05). 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, P0.023 and 6.5 mm Hg, P0.01, 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, P0.004 and 5.8 mm Hg for diastolic, P0.006). 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.