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Nr. 21(4)/2013 DOI:10.2478/rrlm-2013-0042
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The number of PON1 mutant alleles, but not PON1 phenotype, is associated with Gensini score of coronary damage

Irina Ilea, Iulia Lupan, Daniel Corneliu Leucuta, Caius Romulus Duncea, Maria Dronca


Abstract:

Objectives. The aim of this study was to examine the effects of single nucleotide polymorphisms (SNPs) of PON1 gene at the level of promoter region (‒909 and ‒832) and of first exon (+575, A20352G, resulting Q192R substitution) on paraoxonase-1 (PON1) activities in 53 patients with angiographycally proven coronary heart disease (CHD) and 17 free-CHD subjects. Methods and Results. Serum PON1 arylesterase (Ar-ase) and salt-stimulated paraoxonase (ssPO-ase) activities were assessed with manual spectrophotometric methods, by using phenyl acetate and paraoxon as substrates. Common serum biochemical markers were assayed by enzymatic methods using commercial kits, on a Roche/Hitachi 912 Auto Analyzer. PON1 genotypes were determined by PCR and nucleotide sequencing of the amplicons with an ABI PRISMTM 310 Genetic Analyzer and a BigDye® Terminator v3.1 Cycle Sequencing Kit. The severity of coronary artery stenosis was assessed and classified using the Gensini score. We found no significant differences in the PON1 activities and -909(G→C), -832(G→A) and +575(A→G) PON1 polymorphisms between CHD and CHD-free groups. Considering all investigated subjects, we found that -909(G→C) and +575(A→G) SNPs had statistically significant effects on Ar-ase activity and PO- ase activity, respectively. In a multiple regression model we found that diabetes, LDL-cholesterol and the number of mutant alleles were significant independent determinants of the Gensini score. A significant positive correlation was observed only between the Gensini score and the number of mutant alleles. Conclusions. There are no differences between CHD and CHD-free groups regarding PON1 genotypes and phenotypes but the increasing number of PON1 mutant alleles is an important factor in determining the severity of coronary damage.

Keywords: paraoxonase-1,arylesterase,atherosclerosis,Gensini score,genotyping

 
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How to cite
Ilea I, Lupan I, Leucuta DC, Duncea CR, Dronca M. The number of PON1 mutant alleles, but not PON1 phenotype, is associated with Gensini score of coronary damage. Rev Romana Med Lab. 2013;21(4):391-8. DOI:10.2478/rrlm-2013-0042