Hyperhomocysteinemia, paraoxonase activity and risk of coronary artery disease.
OBJECTIVE
Paraoxonase-1 (PON1) detoxifies homocysteine thiolactone (HcyT) in human blood and could thus delay the development of atherosclerosis. We investigated (a) PON1 activity and polymorphisms, and (b) the relationship between PON1 activity, homocysteine (Hcy) and the severity of CAD patients in Tunisian population.


METHODS
We used PCR-RFLP analysis to detect the Q192R and L55M variants of the PON1 gene in 100 patients with CAD and in 120 healthy controls. Paraoxonase activity was measured spectrophotometrically using phenylacetate as a substrate. Total plasma homocysteine concentrations were determined by direct chemiluminescence assay.


RESULTS
We found an increased Hcy level in CAD patients compared to the control group (15.86+/-8.63 vs. 11.9+/-3.25 micromol/L respectively, P<0.001), and a decrease in PON1 activity in CAD patients as compared to the control group (117+/-56 vs. 181+/-73 U/mL respectively, P<0.001). PON1 Q192R and L55M polymorphisms were not associated with the presence of CAD (P=0.592, P=0.294, respectively). However, we found that PON1 activity is lower with the PON1 192RR than with PON1 192QQ genotypes in the study population. Furthermore, there were no association between PON1 L55M polymorphism and PON1 activity. We showed a significant decrease in PON1 activity in CAD patients presenting 0- to 3-vessel stenosis (155+/-39; 135+/-36; 103+/-22; 77+/-24 U/mL, respectively; P<0.001).


CONCLUSIONS
In this study, we showed that low PON1 activity is associated with the PON1 192RR genotypes and associated with the severity of CAD in the Tunisian population. We hypothesize that high level of Hcy together with low PON1 activity results in an increased plasma HcyT plasma concentration leading to protein N-homocysteinylation and the development and progression of atherosclerosis.
Kerkeni
Mohsen
M
Research Unit 03/UR/08-14, Faculty of Pharmacy, Monastir, Tunisia, and Department of Biochemistry, Hospital Saint-Joseph, 75014 Paris, France. m.kerkeni@belgique.com
Addad
Faouzi
F
Chauffert
Maryline
M
Chuniaud
Laurence
L
Miled
Abdelhedi
A
Trivin
François
F
Maaroufi
Khira
K
D000328:Adult; D043303:Aryldialkylphosphatase / Q000097:blood* / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000150:complications* / Q000201:enzymology; D017931:DNA Primers; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications*; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012720:Severity of Illness Index
D017931:DNA Primers; D043303:Aryldialkylphosphatase