A paraoxonase gene polymorphism, PON 1 (55), as an independent risk factor for increased carotid intima-media thickness in middle-aged women.
Paraoxonase (PON) gene polymorphisms have been proposed as genetic markers of risk for cardiovascular disease (CVD). Sporadic results suggest they are correlated with intima-media thickness (IMT), an indicator of preclinical atherosclerotic disease. We have investigated whether polymorphisms PON 1 (M/L) 55, (Q/R) 192, PON 2 (S/C) 311 are related to site-specific carotid plaques in 310 middle-aged women. Subjects were also investigated for physical and biochemical parameters including oxidative markers to evaluate their effect on development of atherosclerotic plaques (IMT>1.2 mm) identified by high resolution B-mode ultrasound. We demonstrate that PON 1 (LL+ML) 55 is associated with plaques both at the bifurcation (OR=2.40; 95% CI 1.00-5.90) and at the common carotid artery (OR=2.75; 95% CI 1.01-7.50), and to the total number of plaques at any site (P<0.05). This polymorphism is an independent parameter with respect to other variables that are significantly associated with plaques, i.e. systolic blood pressure (OR=2.06; 95% CI 1.11-3.81) and oxidized low-density lipoprotein (LDL) antibodies (OR=1.96; 95% CI 1.05-3.69) in cases of common carotid plaques, and lipid peroxides (OR=1.86; 95% CI 1.00-3.50) in cases of bifurcation plaques. In conclusion, PON 1 (LL+ML) 55 but not PON 1 (Q/R) 192 or PON 2 (S/C) 311, appears to be an independent risk factor for increased carotid IMT in middle-aged women.
Fortunato
Giuliana
G
Dipartimento di Biochimica e Biotecnologie Mediche, Università Federico II di Napoli and CEINGE scarl, via S. Pansini 5, Italy.
Rubba
Paolo
P
Panico
Salvatore
S
Trono
Daniela
D
Tinto
Nadia
N
Mazzaccara
Cristina
C
De Michele
Mario
M
Iannuzzi
Arcangelo
A
Vitale
Dino F
DF
Salvatore
Francesco
F
Sacchetti
Lucia
L
D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D043303:Aryldialkylphosphatase; D017536:Carotid Artery, Common; D016893:Carotid Stenosis / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics*; D015331:Cohort Studies; D016001:Confidence Intervals; D004950:Esterases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D016014:Linear Models; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D017539:Tunica Intima / Q000473:pathology*; D018608:Ultrasonography, Doppler
D004950:Esterases; D043303:Aryldialkylphosphatase