Author + information
- Jonathan N. Bella, MD, FACC⁎ ()
- ↵⁎Bronx-Lebanon Hospital Center, 1650 Grand Concourse, 12th Floor, Bronx, New York 10457
I read with great interest the recent article by Bossé et al. (1) that summarized the molecular mechanisms underlying calcific aortic valve disease, the genetic epidemiology of calcific aortic valve disease, and advances in genomic approaches and their applications to elucidating calcific aortic valve disease. Indeed, recent studies have indicated that calcific aortic valve disease is influenced by genetic factors, and the article provided a succinct review of the literature. However, the authors may have “overstated” their assertion that there are no other heritability or inheritance studies that have reported on calcific aortic valve disease other than those reporting on the bicuspid aortic valve. Using an affected sibpair design, we performed genome-wide linkage analysis in African-American and white hypertensive sibships participating in the Hypertension Genetic Epidemiology Network Study and found strong evidence of linkage of aortic valve sclerosis to chromosome 16q22.1–q22.3 (logarithm of odds [LOD] score = 3.1) (2). There was also suggestive evidence of linkage of aortic valve sclerosis to chromosome 19p13.11–p11 (LOD score = 2.88), another position in chromosome 16q22.1–q22.3 (LOD score = 2.63), chromosome 1q42 (LOD score = 2.12), and chromosome 2q37 (LOD score = 2.03). The presence of multiple peaks in several chromosomal regions suggests pleiotropy in susceptibility genes predisposing to aortic valve sclerosis. The study extended the report from Probst et al. (3) that showed clusters of families affected by aortic valve stenosis and that also indicated that offspring of affected individuals had aortic valve sclerosis, suggesting that aortic valve sclerosis may be an early manifestation of familial aortic valve stenosis. Further studies are underway to identify the specific genes contained in these novel chromosomal regions we found in the study that are responsible for the observed linkage results. Although the identification of genes influencing calcific aortic valve disease is challenging, it offers much promise in defining novel mechanistic paradigms and developing therapeutic strategies in the prevention and treatment of calcific aortic valve disease.
- American College of Cardiology Foundation
- Bossé Y.,
- Matthieu P.,
- Pibarot P.
- Probst V.,
- Le Scouarnec S.,
- Legendre A.,
- et al.