Association between a dopamine-4 receptor polymorphism and blood pressure

Srijan Sen, Randolph Nesse, Li Sheng, Scott F. Stoltenberg, Lillian Gleiberman, Margit Burmeister, Alan B. Weder

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Dopamine receptor genes are candidates for hypertension susceptibility. Locally released dopamine increases renal sodium excretion, and defective renal dopamine receptor signaling has been shown to play a role in hypertension. Dopamine-4 receptors are expressed in juxtaglomerular and cortical collecting cells, where dopamine activation could alter sodium and water metabolism and affect blood pressure (BP). The dopamine-4 receptor (DRD4) gene has a 16 amino acid (48 base pairs [bp]) repeat polymorphism located in exon 3 where a G-protein binding area is encoded. The long allele (defined as at least one 7 to 10 repeat) has been associated with the personality trait Novelty Seeking and with substance abuse, but associations between dopamine-4 receptor polymorphisms and BP have not been reported. Methods: We genotyped 479 female and 385 male subjects of white ethnicity at the DRD4 repeat polymorphism site and classified each subject as having either the long or short genotype. Results: We found associations between the DRD4 long allele and increased systolic BP (P = .031), diastolic BP (P = .034), and a history of regular alcohol use (P = .008). Furthermore, for systolic BP (P = .009) and pulse pressure (P = .002), we found evidence for an interaction between dopamine-4 receptor alleles and age, indicating that the effects of dopamine-4 receptor variants on BP increase with age. Conclusion: In this white population, the long variant of the DRD4 gene is associated with a 3-mm Hg higher systolic and 2-mm Hg higher diastolic BP.

Original languageEnglish (US)
Pages (from-to)1206-1210
Number of pages5
JournalAmerican Journal of Hypertension
Volume18
Issue number9
DOIs
StatePublished - Sep 1 2005

Fingerprint

Dopamine Receptors
Blood Pressure
Alleles
Hypertension
Dopamine
Sodium
Genes
GTP-Binding Proteins
Protein Binding
Base Pairing
Substance-Related Disorders
Personality
Exons
Genotype
Alcohols
Kidney
Amino Acids

Keywords

  • Alcohol
  • Blood pressure
  • Dopamine receptor
  • Genetic polymorphism
  • Hypertension
  • Personality

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Association between a dopamine-4 receptor polymorphism and blood pressure. / Sen, Srijan; Nesse, Randolph; Sheng, Li; Stoltenberg, Scott F.; Gleiberman, Lillian; Burmeister, Margit; Weder, Alan B.

In: American Journal of Hypertension, Vol. 18, No. 9, 01.09.2005, p. 1206-1210.

Research output: Contribution to journalArticle

Sen, S, Nesse, R, Sheng, L, Stoltenberg, SF, Gleiberman, L, Burmeister, M & Weder, AB 2005, 'Association between a dopamine-4 receptor polymorphism and blood pressure', American Journal of Hypertension, vol. 18, no. 9, pp. 1206-1210. https://doi.org/10.1016/j.amjhyper.2005.04.010
Sen, Srijan ; Nesse, Randolph ; Sheng, Li ; Stoltenberg, Scott F. ; Gleiberman, Lillian ; Burmeister, Margit ; Weder, Alan B. / Association between a dopamine-4 receptor polymorphism and blood pressure. In: American Journal of Hypertension. 2005 ; Vol. 18, No. 9. pp. 1206-1210.
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AB - Background: Dopamine receptor genes are candidates for hypertension susceptibility. Locally released dopamine increases renal sodium excretion, and defective renal dopamine receptor signaling has been shown to play a role in hypertension. Dopamine-4 receptors are expressed in juxtaglomerular and cortical collecting cells, where dopamine activation could alter sodium and water metabolism and affect blood pressure (BP). The dopamine-4 receptor (DRD4) gene has a 16 amino acid (48 base pairs [bp]) repeat polymorphism located in exon 3 where a G-protein binding area is encoded. The long allele (defined as at least one 7 to 10 repeat) has been associated with the personality trait Novelty Seeking and with substance abuse, but associations between dopamine-4 receptor polymorphisms and BP have not been reported. Methods: We genotyped 479 female and 385 male subjects of white ethnicity at the DRD4 repeat polymorphism site and classified each subject as having either the long or short genotype. Results: We found associations between the DRD4 long allele and increased systolic BP (P = .031), diastolic BP (P = .034), and a history of regular alcohol use (P = .008). Furthermore, for systolic BP (P = .009) and pulse pressure (P = .002), we found evidence for an interaction between dopamine-4 receptor alleles and age, indicating that the effects of dopamine-4 receptor variants on BP increase with age. Conclusion: In this white population, the long variant of the DRD4 gene is associated with a 3-mm Hg higher systolic and 2-mm Hg higher diastolic BP.

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