title: Paraoxonase gene polymorphisms and coronary reactivity in young healthy men.
abstract: This study examined the relationships between paraoxonase genotypes, coronary artery reactivity, and indices of low-density lipoprotein oxidation in healthy men. Impairment in coronary flow reserve, as assessed by positron emission tomography, is associated with lipoprotein oxidation, which is affected by high-density lipoprotein bound enzyme, paraoxonase. Paraoxonase has two common polymorphisms (M/L55 and R/Q192) that change the activity of the enzyme. Forty-nine healthy men (mean age 35 +/- 4 years) were divided by paraoxonase genotype into low (Q192/Q192, or M55/M55, M55/L55) and high-active (R192/Q192, R192/R192, or L55/L55) groups and related to the myocardial blood flow, to the susceptibility of low-density lipoprotein to oxidation, and the autoantibody titer against oxidized low-density lipoprotein. The blood flow was measured by positron emission tomography at rest and during adenosine infusion. The low-active Q192/Q192 genotype was associated with higher resting blood flow corrected for rate-pressure product compared to the high-active R192/R192 and R192/Q192 genotypes (P=0.011). The blood flow stimulated by adenosine was not significantly different in the low- and high-active genotype groups. Paraoxonase genotypes had no effect on low-density lipoprotein susceptibility to oxidation or autoantibody formation against oxidized low-density lipoprotein. Genotypes of paraoxonase may not clearly contribute to the early changes in coronary reactivity. Coronary vasomotor tone at rest appears to be modulated by paraoxonase R/Q192 polymorphism through mechanism(s) unrelated to low-density lipoprotein oxidation.
authors.affiliation: Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Tampere University Hospital and University of Tampere, Medical School, Tampere, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Malin
authors.forename: J
authors.initials: J
authors.lastname: Knuuti
authors.forename: T
authors.initials: T
authors.lastname: Janatuinen
authors.forename: R
authors.initials: R
authors.lastname: Laaksonen
authors.forename: R
authors.initials: R
authors.lastname: Vesalainen
authors.forename: P
authors.initials: P
authors.lastname: Nuutila
authors.forename: H
authors.initials: H
authors.lastname: Jokela
authors.forename: J
authors.initials: J
authors.lastname: Laakso
authors.forename: O
authors.initials: O
authors.lastname: Jaakkola
authors.forename: T
authors.initials: T
authors.lastname: Solakivi
authors.forename: T
authors.initials: T
authors.lastname: Lehtimäki
mesh_terms: D000328:Adult; D001161:Arteriosclerosis / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D043303:Aryldialkylphosphatase; D001783:Blood Flow Velocity / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism; D003326:Coronary Circulation / Q000235:genetics; D003327:Coronary Disease / Q000097:blood / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D003331:Coronary Vessels / Q000201:enzymology / Q000502:physiology; D004950:Esterases / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006339:Heart Rate / Q000235:genetics; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D011110:Polymorphism, Genetic; D014055:Tomography, Emission-Computed; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D004950:Esterases; D043303:Aryldialkylphosphatase