title: Paraoxonase producing PON1 gene M/L55 polymorphism is related to autopsy-verified artery-wall atherosclerosis.
abstract: Paraoxonase (PON) is an antioxidative enzyme, which eliminates lipid peroxides. PON has two common polymorphisms (M/L55 and R/Q192) that influence PON concentration and activity. We studied whether the M/L55 or R/Q192 genotype relates with the severity of atherosclerosis of the abdominal aorta, and the mesenteric and common iliac arteries in 123 consecutive autopsy cases (90 males and 33 females, aged 18-93 years). The severity of atherosclerosis in the arteries was evaluated, and the percentage of stenosis was measured. The intimal thickness in the internal elastic lamina (IEL) of the coeliac (CA), superior mesenteric (SMA) and inferior mesenteric (IMA) arteries were measured by light-microscopy. The LL homozygous men had more atherosclerotic plaques and complicated lesions in the common iliac arteries (56.8%) than the M allele carriers (28.3%, P=0.007). In logistic regression analysis, age (P<0.001) and the PON M/L55 genotype (P=0.015) were associated significantly with the severity of atherosclerosis in the common iliac arteries independent of smoking status, R/Q192 genotype, hypertension, diabetes mellitus, BMI and sex. The mean intima of the IMA was significantly thicker (P=0.035) and the number of stenotic lesions in SMAs significantly higher (P=0.008) in the LL homozygous men than M allele carriers. In turn, the R/Q192 genotype was not statistically significantly associated with plaque type, intimal thickness in the IEL or with the number of stenotic lesions. This study demonstrates that PON L55 homozygosity is an independent risk factor for autopsy-verified atherosclerosis in Finns.
authors.affiliation: Centre for Laboratory Medicine, Department of Clinical Chemistry, Tampere University Hospital and University of Tampere, Medical School, P.O. Box 2000, 33521 Tampere, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Malin
authors.forename: O
authors.initials: O
authors.lastname: Järvinen
authors.forename: T
authors.initials: T
authors.lastname: Sisto
authors.forename: T
authors.initials: T
authors.lastname: Koivula
authors.forename: T
authors.initials: T
authors.lastname: Lehtimäki
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001012:Aorta, Abdominal / Q000473:pathology; D001161:Arteriosclerosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D043303:Aryldialkylphosphatase; D003251:Constriction, Pathologic; D004950:Esterases / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007083:Iliac Artery / Q000473:pathology; D008297:Male; D008638:Mesenteric Arteries / Q000473:pathology; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index
chemical_list: D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human