Association between the paraoxonase-1 192Q>R allelic variant and coronary endothelial dysfunction in patients with early coronary artery disease.
OBJECTIVE
To test the hypothesis that allelic variants of the paraoxonase-1 gene are associated with endothelial dysfunction, an early stage of atherosclerosis.


METHODS
We assessed 192Q>R and 55L>M allelic variants of the paraoxonase gene and coronary endothelial function in response to intracoronary acetylcholine in 99 patients (52 with homozygous QQ, 47 with homozygous RR or heterozygous QR). The study was conducted from September 1, 2002, through November 30, 2004.


RESULTS
Of 52 homozygous QQ patients, 39 (75%) had endothelial dysfunction vs 20 (43%) of the 47 RR/QR patients (P=.001), and this association remained significant after adjustment in a multivariable linear regression model (P=.005). In homozygous QQ vs RR/QR patients, epicardial arterial diameter decreased more (% change in diameter, -22%+/-21% vs -9%+/-16%, respectively, P=.002), coronary blood flow increased less (+37%+/-77% vs +75%+/-75%, P=.02) in response to acetylcholine, and oxidized LDL levels were higher. The 55L>M allelic variant was not significantly associated with endothelial dysfunction and had no effect on the association between endothelial dysfunction and the 192Q>R allelic variant.


CONCLUSIONS
The 192Q>R allelic variant of the paraoxonase-1 gene is associated with coronary endothelial dysfunction. The current study provides further information regarding the potential mechanisms by which this allelic variant contributes to early atherosclerosis in humans.
Lavi
Shahar
S
Division of Cardiovascular Diseases, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
McConnell
Joseph P
JP
Lavi
Ronit
R
Barsness
Gregory W
GW
Rihal
Charanjit S
CS
Novak
Gregory D
GD
Lerman
Lilach O
LO
Lerman
Amir
A
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D022981:Allelic Imbalance / Q000235:genetics*; D043303:Aryldialkylphosphatase / Q000235:genetics*; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics* / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005838:Genotype; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D008077:Lipoproteins, LDL; D014665:Vasodilator Agents; C099252:oxidized low density lipoprotein; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D000109:Acetylcholine