Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis.
Aged
Aortic Valve Stenosis
/ diagnosis
Case-Control Studies
Chromosomes, Human, Pair 9
/ genetics
Coronary Artery Disease
/ diagnosis
Female
Genetic Loci
/ genetics
Genetic Predisposition to Disease
/ genetics
Genetic Variation
/ genetics
Genome-Wide Association Study
/ methods
Humans
Lipoprotein(a)
/ genetics
Male
Middle Aged
Polymorphism, Single Nucleotide
/ genetics
9p21
Aortic valve stenosis
Lipoprotein (a)
Risk factors
Valvular heart disease
Journal
International journal of cardiology
ISSN: 1874-1754
Titre abrégé: Int J Cardiol
Pays: Netherlands
ID NLM: 8200291
Informations de publication
Date de publication:
01 Feb 2019
01 Feb 2019
Historique:
received:
18
03
2018
revised:
14
08
2018
accepted:
15
11
2018
pubmed:
30
11
2018
medline:
28
8
2019
entrez:
29
11
2018
Statut:
ppublish
Résumé
Aortic valve stenosis (AVS) and coronary artery disease (CAD) have a significant genetic contribution and commonly co-exist. To compare and contrast genetic determinants of the two diseases, we investigated associations of the LPA and 9p21 loci, i.e. the two strongest CAD risk loci, with risk of AVS. We genotyped the CAD-associated variants at the LPA (rs10455872) and 9p21 loci (rs1333049) in the GeneCAST (Genetics of Calcific Aortic STenosis) Consortium and conducted a meta-analysis for their association with AVS. Cases and controls were stratified by CAD status. External validation of findings was undertaken in five cohorts including 7880 cases and 851,152 controls. In the meta-analysis including 4651 cases and 8231 controls the CAD-associated allele at the LPA locus was associated with increased risk of AVS (OR 1.37; 95%CI 1.24-1.52, p = 6.9 × 10 Our study confirms the association of the LPA locus with risk of AVS, with a higher effect in those without concomitant CAD. Overall, 9p21 was not associated with AVS.
Sections du résumé
BACKGROUND
BACKGROUND
Aortic valve stenosis (AVS) and coronary artery disease (CAD) have a significant genetic contribution and commonly co-exist. To compare and contrast genetic determinants of the two diseases, we investigated associations of the LPA and 9p21 loci, i.e. the two strongest CAD risk loci, with risk of AVS.
METHODS
METHODS
We genotyped the CAD-associated variants at the LPA (rs10455872) and 9p21 loci (rs1333049) in the GeneCAST (Genetics of Calcific Aortic STenosis) Consortium and conducted a meta-analysis for their association with AVS. Cases and controls were stratified by CAD status. External validation of findings was undertaken in five cohorts including 7880 cases and 851,152 controls.
RESULTS
RESULTS
In the meta-analysis including 4651 cases and 8231 controls the CAD-associated allele at the LPA locus was associated with increased risk of AVS (OR 1.37; 95%CI 1.24-1.52, p = 6.9 × 10
CONCLUSIONS
CONCLUSIONS
Our study confirms the association of the LPA locus with risk of AVS, with a higher effect in those without concomitant CAD. Overall, 9p21 was not associated with AVS.
Identifiants
pubmed: 30482443
pii: S0167-5273(18)31830-8
doi: 10.1016/j.ijcard.2018.11.094
pmc: PMC6878659
mid: NIHMS1054528
pii:
doi:
Substances chimiques
Lipoprotein(a)
0
Types de publication
Journal Article
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
212-217Subventions
Organisme : NHLBI NIH HHS
ID : R35 HL135824
Pays : United States
Organisme : Chief Scientist Office
ID : PCL/17/07
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/16/32/32132
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : ETM/352
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/14/4/30539
Pays : United Kingdom
Informations de copyright
Copyright © 2018. Published by Elsevier B.V.
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