Am J Cardiovasc Dis 2012;2(2):123-132

Original Article
Relationship of PON1 192 and 55 gene polymorphisms to calcific valvular
aortic stenosis

Luis M Moura, Susana Faria, Miguel Brito, Fausto J Pinto, Steen D Kristensen, Isabel M Barros, Nalini Rajamannan,
Francisco Rocha-Gonçalves

Department of Medicine, Oporto School of Medicine, University of Oporto, Portugal; CMAT; Mathematical Research Centre,
Department of Mathematics and Applications, University of Minho, Campus de Azurém, Portugal; Department of Biology,
Technological School of Health, Lisbon Polytechnic Institute, Portugal; Department of Cardiology, Lisbon School of
Medicine, University of Lisbon, Portugal; Department of Cardiology, Aarhus University Hospital, Skejby, Denmark; Pedro
Hispano Hospital, Matosinhos, Portugal; Northwestern School of Medicine, Chicago, IL, USA

Received March 8, 2012; accepted April 22, 2012; Epub May 15, 2012; Published June 15, 2012

Abstract: Introduction and Objectives: Paraoxonases may exert anti-atherogenic action by reducing lipid peroxidation.
Previous studies examined associations between polymorphisms in the paraoxonase 1 (PON1) gene and development of
coronary artery disease (CAD), with inconsistent results. Given the similarities in clinical and pathophysiological risk
factors of CAD and calcific aortic valve stenosis (CAVS), we postulated a link between PON1 alleles and CAVS
progression. Methods: We investigated the association between PON1 55 and 192 single nucleotide polymorphisms
(SNPs), their enzyme activity, and CAVS progression assessed by aortic valve area and transvalvular peak velocity in 67
consecutive patients with moderate CAVS and 251 healthy controls. Results: PON1 paraoxonase activity was higher in
CAVS patients (P<0.001). The PON1 genotype Q192R SNP (P=0.03) and variant allele (R192) (P=0.01) frequencies
differed between CAVS patients and controls. Significant association existed between PON1 enzyme activity, phenotypic
effects of PON1 192 genotype polymorphisms, and CAVS progression, but not between PON1 55 and high-density
lipoprotein (P=0.44) or low-density lipoprotein cholesterol (P=0.12), between 192 genotype and high-density lipoprotein
(P=0.24) or low-density lipoprotein cholesterol (P=0.52). Conclusion: The PON1 genotype Q192R SNP has an important
effect on CAVS disease progression. This study helps outline a genotype-phenotype relationship for PON1 in this unique
population. (AJCD1203003).

Keywords: Calcific aortic stenosis, polymorphism, paraoxonase, atherosclerosis, genetics, association

Address all correspondence to:
Dr. Luis M Moura
Serviço de Medicina A, Faculdade de Medicina da Universidade do Porto
Alameda Prof. Hernani Monteiro; 4200-319, Porto, Portugal.
Tel: +351 225513659; Fax +351226092318
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