APOE alleles are not associated with calcific aortic stenosis

J R Ortlepp ^1*, Manuela Pillich ², Vera Mevissen ², Constanze Krantz ², Melanie Kimmel ², Ruediger Autschbach ³, Georg Langebartels ³, Jeanette Erdmann ⁴, Rainer Hoffmann ² and Klaus Zerres ⁵

¹ Interdisciplinary Intermediate Care University Hospital of Aachen RWTH, Germany
² Medical Clinic I University Hospital of Aachen RWTH, Germany
³ Cardiac Surgery University Hospital of Aachen RWTH, Germany
⁴ Medical Clinic II University Hospital of Schleswig Holstein, Germany
⁵ Institute for Human Genetics University Hospital of Aachen RWTH, Germany

^* To whom correspondence should be addressed. E-mail: jrortlepp{at}ukaachen.de.

Accepted 2 February 2006

Abstract

Background: Previous studies have suggested an association of APOE alleles with degenerative calcific aortic stenosis (AS). However the validity of this association remains uncertain.

Methods: Patients with AS (n=538) and a control group at same age without heart disease (n=536) were recruited. Left heart catherization was performed and mean gradient, aortic valve area (AVA), presence of stenotic coronary artery disease (CAD), and cardiovascular risk factors were assessed (hypercholesterolemia, HLP; hypertension, HTN; smoking, SMO; diabetes mellitus, DM; family history of CAD, FH). The allele frequency of the APOE major alleles 2/3/4 was assessed by genotyping the polymorphisms APOE334 and APOE472 with 5' exonuclease assay (TaqMan(M)).

Results: Mean gradient across the aortic valve in cases was 50 ± 20 mmHg corresponding with a mean AVA of 0.84 ± 0.34 cm². 270 patients with AS had stenotic CAD. Patients with AS and CAD compared to patients with AS without CAD had significantly higher prevalence of HLP (64% vs 40%, p<0.001), SMO (43% vs 27%, p<0.001), DM (27% vs 17%, p<0.01), FH (30% vs 21%, p<0.05), and were more often of male gender (65% vs 44%, p<0.001). The frequency of the major alleles was not different in cases versus controls (APOE 2: 104 (19.3%) vs 94 (17.5%); APOE 3: 319 (59.3%) vs 332 (61.9%); APOE 4: 115 (21.3%) vs 110 (20.5%); all p>0.10).

Conclusion: APOE 4 is not associated with AS reflecting the different genetic background of CAD and AS.

Keywords: aortic stenosis, apoe, polymorphism

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