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(Hypertension. 2000;36:183.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Dopamine D1 Receptor Gene Polymorphism Is Associated With Essential Hypertension

Mikano Sato; Masayoshi Soma; Tomohiro Nakayama; Katsuo Kanmatsuse

From the Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.

Correspondence to Masayoshi Soma, MD, PhD, Second Department of Internal Medicine, Nihon University School of Medicine, 30-1 Ooyaguchi-kamimachi, itabashi-ku, Tokyo 173-8610, Japan. E-mail msoma{at}med.nihon-u.ac.jp

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=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.

Key Words: hypertension, essential • receptors, dopamine • genes • polymorphism

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