Dopamine D1 Receptor Gene Polymorphism Is Associated With Essential Hypertension

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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 (χ 2 =6.5, P =0.01). Multiple logistic linear regression analysis revealed that the genotype frequencies of A/A , A/G , and G/G differed significantly (odds ratio=2.1; 95% CI=1.19 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 ( P <0.01). 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.

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