title: Pilot candidate gene analysis of patients ≥ 60 years old with aortic stenosis involving a tricuspid aortic valve.
abstract: The potential genetic basis of aortic stenosis in older people is poorly understood. A total of 265 patients with aortic stenosis involving tricuspid aortic valves and 961 controls were genotyped for ≤660 candidate single nucleotide polymorphisms (SNPs). After dividing the patients and controls into training and validation sets, we tested the correlation of the SNPs with the age-adjusted aortic valve area, determined by echocardiography or cardiac catheterization. A bootstrapped global p value of ≤0.005 was considered evidence of a possible significant correlation. The cases were aged 73 ± 7 years, and 72.7% were men. The median aortic valve area was 1.0 cm(2) (interquartile range 0.7 to 1.5). The controls were aged 69 ± 6 years, and 69.8% were men. The minor allele frequency was 21% ± 15% (37% <0.20). Three SNPs met the criteria for significant correlation (rs2276288 [MYO7A], p = 0.001; rs5194 [AGTR1], p = 0.004; rs207 307 [ELN], p = 0.005). Another 2 SNPs reached borderline significance (p ≤0.008). In conclusion, we report 3 SNPs to be associated with aortic stenosis involving tricuspid aortic valves in older subjects. Given the concerns regarding the problem of multiple statistical testing, validation studies are required to further assess these correlations.
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA. elliss@ccf.org
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ellis
authors.forename: Sandra
authors.initials: S
authors.lastname: Dushman-Ellis
authors.forename: May M
authors.initials: MM
authors.lastname: Luke
authors.forename: Gurunathan
authors.initials: G
authors.lastname: Murugesan
authors.forename: Kandice
authors.initials: K
authors.lastname: Kottke-Marchant
authors.forename: Gary M
authors.initials: GM
authors.lastname: Ellis
authors.forename: Brian
authors.initials: B
authors.lastname: Griffin
authors.forename: E Murat
authors.initials: EM
authors.lastname: Tuzcu
authors.forename: Stanley
authors.initials: S
authors.lastname: Hazen
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000175:diagnosis / Q000235:genetics*; D006328:Cardiac Catheterization; D004247:DNA / Q000032:analysis*; D018450:Disease Progression; D004452:Echocardiography; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D014261:Tricuspid Valve
chemical_list: D005819:Genetic Markers; D004247:DNA