Parathyroid hormone gene variant and calcific aortic stenosis.
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.
Schmitz
Fabian
F
Division of Cardiology, Pulmonary Diseases, and Vascular Medicine, Department of Medicine, University Hospital RWTH Aachen, Germany.
Ewering
Silke
S
Zerres
Klaus
K
Klomfass
Sebastian
S
Hoffmann
Rainer
R
Ortlepp
Jan R
JR
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
D010281:Parathyroid Hormone; D002118:Calcium