title: The Q192R polymorphism of the paraoxonase 1 gene is a risk factor for coronary artery disease in Saudi subjects.
abstract: Paraoxonase-1 (PON1) is a HDL-bound antioxidant enzyme that protects LDL from oxidative modification. Discovery of the antioxidant properties of PON1 led to extensive research on its role in the initiation and progression of atherosclerosis. The Q192R (rs662; A/G) polymorphism, which results in the glutamine to arginine substitution at position 192, of the PON1 gene has been linked to increased atherosclerosis risk in several but not all population studies. Besides genetic factors, environmental variables and ethnicity have been implicated as factors responsible for the ambiguity in relating the PON1 gene with atherosclerotic risk. Here, we tested the association of the Q192R polymorphism with coronary artery disease (CAD) in Saudi ethnic subjects taking environmental factors into consideration. The genomic DNA samples from 121 angiographically confirmed CAD cases and 108 normal healthy control subjects were genotyped by PCR-RFLP analysis. The distribution of QQ, QR, and RR genotypes was significantly different between cases and controls (p < 0.005). The RR genotype was associated with CAD risk independently of several established risk factors including age, gender, smoking, obesity, and diabetes (OR 2.2, 1.4-7.4, p < 0.01). Genotype-based stratification of demographic and biochemical data revealed that the RR genotype has proatherogenic properties. This study, thus, identifies the Q192R polymorphism as an additional risk factor for CAD in the Saudi population and suggests that it may have prognostic value. The negative effect of this genetic variant is presumably due to the diminished ability of the RR variant genotype of PON1 to blunt LDL oxidation.
authors.affiliation: Department of Biochemistry College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Hassan
authors.forename: Omar S
authors.initials: OS
authors.lastname: Al-Attas
authors.forename: Tajamul
authors.initials: T
authors.lastname: Hussain
authors.forename: Nasser M
authors.initials: NM
authors.lastname: Al-Daghri
authors.forename: Majed S
authors.initials: MS
authors.lastname: Alokail
authors.forename: Abdul K
authors.initials: AK
authors.lastname: Mohammed
authors.forename: Benjamin
authors.initials: B
authors.lastname: Vinodson
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D043303:Aryldialkylphosphatase / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012307:Risk Factors; D012529:Saudi Arabia; D014280:Triglycerides / Q000097:blood
chemical_list: D014280:Triglycerides; D002784:Cholesterol; D043303:Aryldialkylphosphatase