Dopamine D1 Receptor Gene Polymorphism Is Associated With Essential Hypertension

Abstract

Abstract-Dopamine has been shown to influence renal sodium excretion through a direct interaction with the dopamine receptor (DR). The dopamine D1 receptor (DRD1) has been localized to the proximal tubules and is known to increase sodium excretion by inhibiting Na-H exchanger and Na,K-ATPase activity. Defective renal dopamine production and/or DR function have been reported in essential hypertension (EH) as well as in genetic models of animal hypertension. With a restriction fragment length polymorphism of the DRD1 gene, we performed an association study in patients with EH. One hundred thirty-one subjects with EH and 136 age-matched normotensive (NT) controls were studied. Polymerase chain reaction was used to amplify the A-48G polymorphic site in the DRD1 gene, and restriction analysis of the polymerase chain reaction product was used to score the A and G alleles. The allele frequencies in the EH group and NT group were then compared. The G allele was observed more frequently in the EH group than in the NT group, and the allele frequencies in the 2 groups differed significantly ( 2 ϭ6.5, Pϭ0.01). Multiple logistic linear regression analysis revealed that the genotype frequencies of A/A, A/G, and G/G differed significantly (odds ratioϭ2.1; 95% CIϭ1.19 to 3.66) between the EH and NT groups. EH patients who possess the G allele had a higher diastolic blood pressure than those lacking the G allele (PϽ0.01). Thus, the alleles detected by this restriction fragment length polymorphism in the DRD1 gene are associated with EH, and they appear to influence the diastolic blood pressure of Japanese EH patients.

Blood Pressure and Renal Sodium Handling in Relation to Genetic Variation in the DRD1 Promoter and GRK4

“…Finally, in humans, juxtaglomerular cells do not express DRD1, 23 and selective D1-like receptor stimulation has no significant effects on plasma renin activity. 24 In keeping with our current findings, in the aforementioned Japanese study, 18 plasma renin activity and the plasma aldosterone concentration were not associated with the DRD1 genotype in 90 untreated hypertensive patients.…”

“…However, the sib-pair transmission disequilibrium test, involving 39 informative twin pairs for AϪ48G, did not reveal any significant association with systolic or diastolic blood pressure. 17 In a Japanese study 18 of 131 hypertensive patients and 136 normotensive controls, the allele frequencies of AϪ48G substantially deviated from those observed in whites, amounting to 0.92/0.08 in the normotensive controls and 0.84/0.16 in the hypertensive patients. In this study, 18 the DRD1 Ϫ48G allele was more frequent in hypertensive patients than normoten- …”

“…18 Moreover, among untreated hypertensive patients, Ϫ48G allele carriers had a higher diastolic blood pressure than Ϫ48AA homozygotes. 18 In the current study, we observed that RNa dist , but not RNa prox , was associated with variation in the DRD1 gene. Most experimental and clinical studies suggest that DRD1 primarily affects proximal tubular sodium reabsorption.…”

Single-Nucleotide Polymorphisms for Diagnosis of Salt-Sensitive Hypertension

“…AGT A-6G, ACE I/D, ADD, and D 1 R were genotyped as reported (23,26,39,40 ). No variations for 11␤HSD2 G534A, GRK4 V247I, GRK4 A253T, or GRK4 G562D were detected; thus, these variants were not included in subsequent analyses.…”

Dopamine, hypertension and obesity

“…21 In this regard, the presence of polymorphic forms of the D 1 codifying gene has been described in patients with essential AHT. 26 The D 5 /D 1 ratio in nephron is insignificant, therefore DA actions related to the D 1 (D 1 -like) family are normally attributed to D 1 . 24,27 As far as D 2 -like receptors are concerned, D 3 is expressed in proximal tubules and juxtaglomerular cells.…”