Pilot Candidate Gene Analysis of Patients ≥60 Years Old With Aortic Stenosis Involving a Tricuspid Aortic Valve

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 cm2 (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.