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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 7,880 cases and 851,152 controls.
Results: In the meta-analysis including 4,651 cases and 8,231 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=6.9x10-10) with a larger effect size in those without CAD (OR 1.53; 95%CI 1.31-1.79) compared to those with CAD (OR 1.27; 95%CI 1.12-1.45). The CAD-associated allele at 9p21 was associated with a trend towards lower risk of AVS (OR 0.93; 95%CI 0.88-0.99, p=0.014). External validation confirmed the association of the LPA risk allele with risk of AVS (OR 1.37; 95%CI 1.27-1.47), again with a higher effect size in those without CAD. The small protective effect of the 9p21 CAD risk allele could not be replicated (OR 0.98; 95%CI 0.95-1.02).
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.
- Aortic valve stenosis
- Lipoprotein (a)
- Risk factors
- Valvular heart disease
- Chromosomes, Human, Pair 9/genetics
- Middle Aged
- Aortic Valve Stenosis/diagnosis
- Genetic Predisposition to Disease/genetics
- Genetic Variation/genetics
- Case-Control Studies
- Coronary Artery Disease/diagnosis
- Polymorphism, Single Nucleotide/genetics
- Genome-Wide Association Study/methods
- Genetic Loci/genetics
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Moving Towards a New Personalised Medicine Approach to Primary Prevention in Diabetes: The First Steps
5/08/15 → 4/09/17