title: Serum paraoxonase-1 (PON1) activities (PONase/AREase) and polymorphisms in patients with type 2 diabetes mellitus in a North-West Indian population.
abstract: OBJECTIVE
  Paraoxonase-1 (PON1), an HDL-C associated enzyme, protects lipoproteins from oxidation. There is evidence that PON1 enzyme activity is reduced in the patients with type 2 diabetes mellitus (T2DM). North-West Indian Punjabis, a distinct ethnic group has high incidence of T2DM. However till date there is no information regarding PON1 enzyme activities and PON1 polymorphisms in T2DM patients of this ethnic group.
  
  
  METHODS
  We identified polymorphisms in the coding Q192R, L55M and promoter -909G/C, -162A/G, -108C/T of the PON1 gene by using PCR-RFLP, multiplex PCR and allele specific oligonucleotide PCR assays in 250 T2DM patients and 300 healthy controls. We also assessed paraoxonase (PONase) and arylesterase (AREase) activities of PON1 enzyme.
  
  
  RESULTS
  The serum PONase (114.2 vs. 178.0nmol/min/ml) and AREase (62.7 vs. 82.5μmol/min/ml) activities were significantly lower (p<0.0001) in patients as compared to controls. PONase activity was affected by all the studied PON1 polymorphisms. However, AREase activity was not affected by any of these polymorphisms. Coding Q192R and promoter -909G/C polymorphisms showed significant differences in genotypic distribution. QR, RR (Q192R) and GC, CC (-909G/C) genotypes and L-C-A-R-G, L-T-A-R-G, L-T-G-Q-C haplotypes showed significant association with type 2 diabetes. No significant linkage disequilibrium was observed among the five polymorphisms.
  
  
  CONCLUSIONS
  Both PONase and AREase activities are lower in patients and this could lead to increased lipid peroxidation and accelerated atherosclerosis in them. PONase activity, but not AREase activity is influenced by PON1 polymorphisms. QR, RR, GC, CC genotypes and L-C-A-R-G, L-T-A-R-G, L-T-G-Q-C haplotypes are commoner in diabetics as compared to controls and may be related to genetic susceptibility to type 2 diabetes.
authors.affiliation: Department of Biochemistry, PGIMER, Chandigarh, India. nidhi005@gmail.com
authors.forename: Nidhi
authors.initials: N
authors.lastname: Gupta
authors.forename: B K
authors.initials: BK
authors.lastname: Binukumar
authors.forename: Surjit
authors.initials: S
authors.lastname: Singh
authors.forename: Aditya
authors.initials: A
authors.lastname: Sunkaria
authors.forename: Ramesh
authors.initials: R
authors.lastname: Kandimalla
authors.forename: Anil
authors.initials: A
authors.lastname: Bhansali
authors.forename: Kiran Dip
authors.initials: KD
authors.lastname: Gill
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D043303:Aryldialkylphosphatase / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007194:India; D016014:Linear Models; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D008076:Cholesterol, HDL; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human