Association of G-protein-coupled receptor kinase 4 haplotypes, but not HSD3B1 or PTP1B polymorphisms, with essential 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 GRK4gamma variants (R65L, A142V and A486V), one HSD3B1 variant (T-->C Leu(338)) and one PTP1B variant (1484insG) were genotyped by polymerase chain reaction and restriction enzyme digestion or by homogenous MassEXTEND(TM) 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. Conclusion: Genetic variation in GRK4gamma was associated with HT in the subjects studied. (C) 2004 Lippincott Williams Wilkins.