title: Parathyroid hormone gene variant and calcific aortic stenosis.
abstract: OBJECTIVE
  Calcific aortic stenosis (AS) is the most frequently acquired valvular disease of the elderly in the Western world. A genetic background for AS has been proposed. The deposition of calcium hydroxyapatite is the key problem of valve calcification; vitamin D and parathyroid hormone are major factors in calcium homeostasis. The vitamin D receptor (VDR) gene and parathyroid hormone (PTH) gene variants were selected as candidate genes.
  
  
  METHODS
  A total of 538 patients with severe calcific AS (identified echocardiographically) were characterized by left heart catheterization. A group of 536 patients in whom heart disease had been excluded by left heart catheterization served as a control population. The cardiovascular risk profile was assessed, and three gene variants were analyzed, namely VDR rs1544410, VDR rs1073810, and PTH rs6254.
  
  
  RESULTS
  Patients with AS were found to have a higher prevalence of the PTH AA genotype (108 +/- 20.1% versus 71 +/- 13.2%; p = 0.007), while the VDR gene revealed a marginal, but statistically non-significant, association. The age and risk profile was similar in both groups.
  
  
  CONCLUSIONS
  To date, the association of the PTH gene variant has been the only positive association studied in patients with AS in a large population. Hence, the polymorphism is within an intron; the molecular mechanisms of altered gene expression should undergo further investigation.
authors: Division of Cardiology, Pulmonary Diseases, and Vascular Medicine, Department of Medicine, University Hospital RWTH Aachen, Germany.
authors: Fabian
authors: F
authors: Schmitz
authors: Silke
authors: S
authors: Ewering
authors: Klaus
authors: K
authors: Zerres
authors: Sebastian
authors: S
authors: Klomfass
authors: Rainer
authors: R
authors: Hoffmann
authors: Jan R
authors: JR
authors: Ortlepp
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000235:genetics* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D010281:Parathyroid Hormone / Q000235:genetics* / Q000378:metabolism
chemical_list: D010281:Parathyroid Hormone; D002118:Calcium