PMID- 21803130 OWN - NLM STAT- MEDLINE DCOM- 20111202 LR - 20220408 IS - 1879-0038 (Electronic) IS - 0378-1119 (Linking) VI - 487 IP - 1 DP - 2011 Nov 1 TI - Serum paraoxonase-1 (PON1) activities (PONase/AREase) and polymorphisms in patients with type 2 diabetes mellitus in a North-West Indian population. PG - 88-95 LID - 10.1016/j.gene.2011.07.011 [doi] AB - 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. 82.5mumol/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. CONCLUSION: 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. CI - Copyright (c) 2011 Elsevier B.V. All rights reserved. FAU - Gupta, Nidhi AU - Gupta N AD - Department of Biochemistry, PGIMER, Chandigarh, India. nidhi005@gmail.com FAU - Binukumar, B K AU - Binukumar BK FAU - Singh, Surjit AU - Singh S FAU - Sunkaria, Aditya AU - Sunkaria A FAU - Kandimalla, Ramesh AU - Kandimalla R FAU - Bhansali, Anil AU - Bhansali A FAU - Gill, Kiran Dip AU - Gill KD LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110726 PL - Netherlands TA - Gene JT - Gene JID - 7706761 RN - 0 (Cholesterol, HDL) RN - EC 3.1.1.- (Carboxylic Ester Hydrolases) RN - EC 3.1.1.2 (arylesterase) RN - EC 3.1.8.1 (Aryldialkylphosphatase) RN - EC 3.1.8.1 (PON1 protein, human) SB - IM MH - Adult MH - Amino Acid Sequence MH - Amino Acid Substitution MH - Aryldialkylphosphatase/blood/*genetics/metabolism MH - Carboxylic Ester Hydrolases/metabolism MH - Case-Control Studies MH - Cholesterol, HDL/blood MH - Diabetes Mellitus, Type 2/blood/enzymology/*genetics MH - Female MH - Gene Frequency MH - Genetic Predisposition to Disease MH - Genotype MH - Haplotypes MH - Humans MH - India MH - Linear Models MH - Linkage Disequilibrium MH - Male MH - Middle Aged MH - Multivariate Analysis MH - Polymerase Chain Reaction MH - Polymorphism, Restriction Fragment Length MH - *Polymorphism, Single Nucleotide MH - Promoter Regions, Genetic/*genetics EDAT- 2011/08/02 06:00 MHDA- 2011/12/13 00:00 CRDT- 2011/08/02 06:00 PHST- 2011/06/22 00:00 [received] PHST- 2011/07/09 00:00 [accepted] PHST- 2011/08/02 06:00 [entrez] PHST- 2011/08/02 06:00 [pubmed] PHST- 2011/12/13 00:00 [medline] AID - S0378-1119(11)00332-5 [pii] AID - 10.1016/j.gene.2011.07.011 [doi] PST - ppublish SO - Gene. 2011 Nov 1;487(1):88-95. doi: 10.1016/j.gene.2011.07.011. Epub 2011 Jul 26.