Turk Kardiyol Dern Ars. 2009; 37(7): 473-478

The relationship between paraoxanase gene Leu-Met (55) and Gln-Arg (192) polymorphisms and coronary artery disease

Pınar Taşkıran¹, Sırrı F Çam¹, Cevat Şekuri², Nurullah Tüzün³, Emin Alioğlu³, Nuray Altıntaş⁴, Afig Berdeli^4
1Celal Bayar University, Scholl Of Medicine, Department Of Biology And Genetics,manisa
²Kent Hospital, Department Of Cardiology, Izmir
³Central Hospital, Department Of Cardiology, Izmir
⁴Ege University, Department Of Pediatry, Izmir

OBJECTIVES
Paraoxonase (PON1) is a high-density lipoprotein (HDL)-associated esterase that hydrolyses lipoperoxides. PON1 serves as a protective factor against oxidative modification of LDL, suggesting that it may play an important role in the prevention of atherosclerotic process. Research has focused on two polymorphisms: leucine (L allele) to methionine (M allele) substitution at codon 55, and glutamine (A allele) to arginine (B allele) substitution at codon 192.

STUDY DESIGN
We examined amino acid changes at codon 55 and 192 in the PON1 gene by polymerase chain reaction and using restriction enzymes in 120 patients (92 men, 28 women; mean age 48.2±4.3 years) with premature coronary artery disease (CAD) and in 102 healthy subjects (80 men, 22 women; mean age 46.8±5.2 years) with no history of CAD and a normal electrocardiogram.

RESULTS
Distribution of genotypes in the patient and control groups at codon 55 were 6.7% and 4.9% for MM, 46.7% and 29.4% for LM, 46.7% and 65.7% for LL, respectively. The frequency of genotypes at codon 192 were as follows: 4.2% and 2% for RR, 40% and 35.3% for QR, and 55.8% and 62.8% for QQ, respectively. While the frequency of PON1 55M allele was higher in the CAD group (0.3 vs. 0.2), PON1 192R allele frequency did not differ (0.2). There was a significant relationship between the PON1 M/L55 polymorphism and CAD (p=0.017), whereas the R/Q192 polymorphism was not associated with CAD (p=0.445).

CONCLUSION
These data suggest that the PON1 M/L55 polymorphism shows a significant relationship with CAD and the Q/R192 polymorphism is not a major risk factor causing susceptibility to CAD in our population.

Keywords: Cholesterol, HDL/metabolism, coronary artery disease/ enzymology/genetics; esterases/genetics; genotype; paraoxon/ metabolism; polymerase chain reaction; polymorphism, genetic.

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