title: Vitamin D receptor genetics on extracellular matrix biomarkers and hemodynamics in systolic heart failure.
abstract: BACKGROUND
  Vitamin D deficiency has been associated with the development of myocardial hypertrophy and inflammation. These findings suggest that vitamin D status and vitamin D receptor (VDR) genomics may play a role in myocardial fibrosis. The aim of this pilot study was to determine the association between vitamin D levels, VDR polymorphisms, and biomarkers of left ventricular remodeling and hemodynamics.
  
  
  METHODS
  In a cross-sectional pilot study, patients with ejection fraction (EF) <40% (and New York Heart Association ≥ II) undergoing right heart catheterization were included in the study. Blood was collected for determination of 25-hydroxyvitamin D level (antibody competitive immunoassay), VDR genotypes (BsmI, ApaI, TaqI, and FokI), and biomarkers (N-terminal propeptide of collagen type III [PIIINP], matrix metalloproteinase 2, and galectin 3). The vitamin D genotypes were determined through the use of pyrosequencing.
  
  
  RESULTS
  A total of 30 patients with a mean EF of 17% ± 8% were enrolled. There was a significant association between the BsmI C allele, ApaI G allele, and TaqI A allele, which formed a haplotype block (CGA) for analysis. There were no differences in baseline parameters between patients with the VDR haplotype block (n = 20) and those without (n = 10). Individual genotypes were not associated with any biomarker or hemodynamics. Patients with the CGA haplotype demonstrated significantly higher log PIIINP values (1.74 ± 0.32 mcg/mL vs 1.36 ± 0.31 mcg/mL, P = .0041). When evaluating vitamin D levels below and above the median level (19 ng/mL), there was no significant difference between these 2 groups in regard to biomarker levels for left ventricular remodeling.
  
  
  CONCLUSIONS
  This study has shown that a biomarker for collagen type III synthesis, PIIINP, was associated with the CGA haplotype of BsmI, ApaI, and TaqI single nucleotide polymorphisms on the VDR. These findings suggest that VDR genetics may play a role in myocardial fibrosis in patients with systolic heart failure.
authors: Department of Pharmacy Services, University of Michigan Health System, Ann Arbor, Michigan, USA.
authors: Michael P
authors: MP
authors: Dorsch
authors: Department of Pharmacy Services, Henry Ford Hospital, Detroit, MI, USA.
authors: Carrie W
authors: CW
authors: Nemerovski
authors: Department of Clinical and Social Administrative Sciences, University of Michigan, College of Pharmacy, Ann Arbor, MI, USA.
authors: Vicki L
authors: VL
authors: Ellingrod
authors: St Vincent Heart Center of Indiana, Indianapolis, IN, USA.
authors: Jennifer A
authors: JA
authors: Cowger
authors: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Health Systems, Ann Arbor, MI, USA.
authors: D Bradley
authors: DB
authors: Dyke
authors: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Health Systems, Ann Arbor, MI, USA.
authors: Todd M
authors: TM
authors: Koelling
authors: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Health Systems, Ann Arbor, MI, USA.
authors: Audrey H
authors: AH
authors: Wu
authors: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Health Systems, Ann Arbor, MI, USA.
authors: Keith D
authors: KD
authors: Aaronson
authors: Department of Pharmacology, University of Michigan, Medical School, Ann Arbor, MI, USA.
authors: Robert U
authors: RU
authors: Simpson
authors: Department of Clinical and Social Administrative Sciences, University of Michigan, College of Pharmacy, Ann Arbor, MI, USA bbleske@umich.edu.
authors: Barry E
authors: BE
authors: Bleske
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D005355:Fibrosis; D005838:Genotype; D006239:Haplotypes; D054143:Heart Failure, Systolic / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D018167:Receptors, Calcitriol / Q000097:blood / Q000235:genetics*; D014807:Vitamin D / Q000097:blood / Q000235:genetics; D014808:Vitamin D Deficiency
chemical_list: D015415:Biomarkers; D018167:Receptors, Calcitriol; D014807:Vitamin D
keywords: biomarkers; hemodynamics; systolic heart failure; vitamin D