title: Association between a dopamine-4 receptor polymorphism and blood pressure.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neuroscience Program, University of Michigan, Ann Arbor, MI 48106, USA.
authors.forename: Srijan
authors.initials: S
authors.lastname: Sen
authors.forename: Randolph
authors.initials: R
authors.lastname: Nesse
authors.forename: Li
authors.initials: L
authors.lastname: Sheng
authors.forename: Scott F
authors.initials: SF
authors.lastname: Stoltenberg
authors.forename: Lillian
authors.initials: L
authors.lastname: Gleiberman
authors.forename: Margit
authors.initials: M
authors.lastname: Burmeister
authors.forename: Alan B
authors.initials: AB
authors.lastname: Weder
mesh_terms: D000328:Adult; D000367:Age Factors; D000483:Alleles; D001794:Blood Pressure / Q000502:physiology*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D011110:Polymorphism, Genetic; D050638:Receptors, Dopamine D4 / Q000235:genetics*
chemical_list: D050638:Receptors, Dopamine D4