title: The Fok1 vitamin D receptor gene polymorphism is associated with plasma renin activity in Caucasians.
abstract: OBJECTIVE
  25-Hydroxyvitamin D (25(OH)D) deficiency and excess activity of the renin-angiotensin system (RAS) are both associated with cardiovascular disease. Vitamin D interacts with the vitamin D receptor (VDR) to negatively regulate renin expression in mice; however, human studies linking genetic variation in the VDR with renin are lacking. We evaluated (i) whether genetic variation in the VDR at the Fok1 polymorphism was associated with plasma renin activity (PRA) in a population of hypertensives and a separate population of normotensives and (ii) whether the association between Fok1 genotype and PRA was independent of 25(OH)D levels.
  
  
  METHODS
  Genetic association study, assuming an additive model of inheritance, of 375 hypertensive and 146 normotensive individuals from the HyperPATH cohort, who had PRA assessments after 1 week of high dietary sodium balance (HS) and l week of low dietary sodium balance (LS).
  
  
  RESULTS
  The minor allele (T) at the Fok1 polymorphism was significantly associated with lower PRA in hypertensives (LS: β = -0·22, P < 0·01; HS: β = -0·19, P < 0·01); when repeated in normotensives, a similar relationship was observed (LS: β = -0·17, P < 0·05; HS: β = -0·18, P = 0·14). In multivariable analyses, both higher 25(OH)D levels and the T allele at Fok1 were independently associated with lower PRA in hypertensives; however, 25(OH)D was not associated with PRA in normotensives.
  
  
  CONCLUSIONS
  Genetic variation at the Fok1 polymorphism of the VDR gene, in combination with 25(OH)D levels, was associated with PRA in hypertension. These findings support the vitamin D-VDR complex as a potential regulator of renin activity in humans.
authors.affiliation: Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. avaidya1@partners.org
authors.forename: Anand
authors.initials: A
authors.lastname: Vaidya
authors.forename: Bei
authors.initials: B
authors.lastname: Sun
authors.forename: John P
authors.initials: JP
authors.lastname: Forman
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Brown
authors.forename: Nikheel S
authors.initials: NS
authors.lastname: Kolatkar
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Williams
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Williams
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000209:etiology / Q000235:genetics; D016014:Linear Models; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D012083:Renin / Q000097:blood*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000009:adverse effects; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D044465:White People / Q000235:genetics*
chemical_list: D018167:Receptors, Calcitriol; D017673:Sodium Chloride, Dietary; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D012083:Renin