title: Paraoxonase 1 (PON1) polymorphisms, haplotypes and activity in predicting cad risk in North-West Indian Punjabis.
abstract: BACKGROUND
  Human serum paraoxonase-1 (PON1) prevents oxidation of low density lipoprotein cholesterol (LDL-C) and hydrolyzes the oxidized form, therefore preventing the development of atherosclerosis. The polymorphisms of PON1 gene are known to affect the PON1 activity and thereby coronary artery disease (CAD) risk. As studies are lacking in North-West Indian Punjabi's, a distinct ethnic group with high incidence of CAD, we determined PON1 activity, genotypes and haplotypes in this population and correlated them with the risk of CAD.
  
  
  RESULTS
  350 angiographically proven (≥ 70% stenosis) CAD patients and 300 healthy controls were investigated. PON1 activity was determined towards paraoxon (Paraoxonase; PONase) and phenylacetate (Arylesterase; AREase) substrates. In addition, genotyping was carried out by using multiplex PCR, allele specific oligonucleotide -PCR and PCR-RFLP methods and haplotyping was determined by PHASE software. The serum PONase and AREase activities were significantly lower in CAD patients as compared to the controls. All studied polymorphisms except L55M had significant effect on PONase activity. However AREase activity was not affected by them. In a logistic regression model, after adjustment for the conventional risk factors for CAD, QR (OR: 2.73 (1.57-4.72)) and RR (OR, 16.24 (6.41-41.14)) genotypes of Q192R polymorphism and GG (OR: 2.07 (1.02-4.21)) genotype of -162A/G polymorphism had significantly higher CAD risk. Haplotypes L-T-G-Q-C (OR: 3.25 (1.72-6.16)) and L-T-G-R-G (OR: 2.82 (1.01-7.80)) were also significantly associated with CAD.
  
  
  CONCLUSIONS
  In conclusion this study shows that CAD patients had lower PONase and AREase activities as compared to the controls. The coding Q192R polymorphism, promoter -162A/G polymorphism and L-T-G-Q-C and L-T-G-R-G haplotypes are all independently associated with CAD.
authors.affiliation: Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Gupta
authors.forename: Surjit
authors.initials: S
authors.lastname: Singh
authors.forename: V Nagarjuna
authors.initials: VN
authors.lastname: Maturu
authors.forename: Yash Paul
authors.initials: YP
authors.lastname: Sharma
authors.forename: Kiran Dip
authors.initials: KD
authors.lastname: Gill
mesh_terms: D000328:Adult; D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D010261:Paraoxon / Q000378:metabolism; D010648:Phenylacetates / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors
chemical_list: D010648:Phenylacetates; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; C025136:phenylacetic acid; D010261:Paraoxon