Association between the paraoxonase-1 192Q>R allelic variant and coronary endothelial dysfunction in patients with early coronary artery disease

Shahar Lavi, Joseph P. McConnell, Ronit Lavi, Gregory W. Barsness, Charanjit S. Rihal, Gregory D. Novak, Lilach O Lerman, Amir Lerman

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Abstract

OBJECTIVE: To test the hypothesis that allelic variants of the paraoxonase-1 gene are associated with endothelial dysfunction, an early stage of atherosclerosis. PATIENTS AND 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 (percent 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. CONCLUSION: 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.

Original languageEnglish (US)
Pages (from-to)158-164
Number of pages7
JournalMayo Clinic Proceedings
Volume83
Issue number2
DOIs
StatePublished - 2008

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Aryldialkylphosphatase
Coronary Artery Disease
Acetylcholine
Linear Models
Atherosclerosis
Genes

ASJC Scopus subject areas

  • Medicine(all)

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Association between the paraoxonase-1 192Q>R allelic variant and coronary endothelial dysfunction in patients with early coronary artery disease. / Lavi, Shahar; McConnell, Joseph P.; Lavi, Ronit; Barsness, Gregory W.; Rihal, Charanjit S.; Novak, Gregory D.; Lerman, Lilach O; Lerman, Amir.

In: Mayo Clinic Proceedings, Vol. 83, No. 2, 2008, p. 158-164.

Research output: Contribution to journalArticle

Lavi, Shahar ; McConnell, Joseph P. ; Lavi, Ronit ; Barsness, Gregory W. ; Rihal, Charanjit S. ; Novak, Gregory D. ; Lerman, Lilach O ; Lerman, Amir. / Association between the paraoxonase-1 192Q>R allelic variant and coronary endothelial dysfunction in patients with early coronary artery disease. In: Mayo Clinic Proceedings. 2008 ; Vol. 83, No. 2. pp. 158-164.
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abstract = "OBJECTIVE: To test the hypothesis that allelic variants of the paraoxonase-1 gene are associated with endothelial dysfunction, an early stage of atherosclerosis. PATIENTS AND 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 (percent 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. CONCLUSION: 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.",
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AU - McConnell, Joseph P.

AU - Lavi, Ronit

AU - Barsness, Gregory W.

AU - Rihal, Charanjit S.

AU - Novak, Gregory D.

AU - Lerman, Lilach O

AU - Lerman, Amir

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N2 - OBJECTIVE: To test the hypothesis that allelic variants of the paraoxonase-1 gene are associated with endothelial dysfunction, an early stage of atherosclerosis. PATIENTS AND 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 (percent 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. CONCLUSION: 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.

AB - OBJECTIVE: To test the hypothesis that allelic variants of the paraoxonase-1 gene are associated with endothelial dysfunction, an early stage of atherosclerosis. PATIENTS AND 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 (percent 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. CONCLUSION: 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.

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