Serum paraoxonase (PON1) 55 and 192 polymorphism and paraoxonase activity and concentration in non-insulin dependent diabetes mellitus

Mackness, Bharti; Mackness, Michael I.; Arrol, Sharon; Turkie, Wajdi; Julier, K.; Abuasha, Bashir; Miller, John E.; Boulton, Andrew J.M.; Durrington, Paul N.

doi:10.1016/s0021-9150(98)00095-1

Cited by 250 publications

(197 citation statements)

References 21 publications

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“…We found a 40 % decrease in PON activity in a group of Type II diabetic subjects with CAD compared with a group of non-diabetic subjects with CAD. Decreased PON in patients with Type II diabetes and CAD have also been found [44,45]. Polymorphisms within the PON gene that are prevalent in Type II diabetic patients with CAD have been reported [7,46].…”

Section: Discussionmentioning

confidence: 96%

Glycation impairs high-density lipoprotein function

et al. 2000

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Section: Discussionmentioning

confidence: 96%

Glycation impairs high-density lipoprotein function

et al. 2000

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“…All genotyping was conducted by polymerase chain reaction (PRC) amplification followed by polymorphism-specific restriction digestion and gel electrophoresis. The two PON1 coding-region (L55M and Q192R) and two PON1 regulatory-region (T-108C and G-909C) polymorphisms were determined, as described previously (Mackness et al 1998a(Mackness et al , 1998bBrophy et al 2001). Each genotype was read by two people independently.…”

Section: Determination Of Pon1 Genotypesmentioning

confidence: 99%

“…The PON1 L55M polymorphism has not been demonstrated to affect the relative rates of hydrolysis of different substrates (Adkin et al 1993;Humbert et al 1993). However, the M allele is associated with lower PON1 activity, PON1 protein and PON1 mRNA levels (Blatter et al 1997;Leviev et al 1997;Mackness et al 1998a;Brophy et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Paraoxonase 1 status in the Thai population

et al. 2005

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Human serum paraoxonase 1 (PON1), a highdensity lipoprotein (HDL)-associated enzyme, has been shown to reduce the oxidation of low-density lipoprotein (LDL) and HDL by degrading lipid peroxides. This property of PON1 accounts for its ability to protect against atherosclerosis. In this study, we identified four polymorphisms in both the coding (L55M and Q192R) and regulatory regions (T-108C and G-909C) of the human PON1 gene in 202 healthy Thai individuals and investigated the influence of these polymorphisms on serum PON1 activity towards three substrates, namely, paraoxon, phenylacetate and diazoxon. The PON1 L55M, Q192R and G-909C polymorphisms significantly affected the variation in serum PON1 activity towards paraoxon. Serum PON1 activity towards paraoxon was significantly different among the genotype groups, as follows: 55LL > 55LM/55MM, 192RR > 192QR > 192QQ and À909CC > À909CG > À909GG. The PON1 Q192R and G-909C polymorphisms also influenced the variation in serum PON1 activity towards diazoxon but in the opposite direction to the activity towards paraoxon. Only the PON1 L55M polymorphism was associated with significant variation in serum PON1 activity towards phenylacetate while the PON1 T-108C polymorphism had no significant effect on serum PON1 activity towards any substrate. We also found linkage disequilibrium among the polymorphic sites, including Q192R versus L55M, Q192R versus T-108C and Q192R versus G-909C. Serum PON1 activity towards both paraoxon and phenylacetate, but not diazoxon, was positively correlated with HDL cholesterol (HDL-C) and apo AI concentrations. None of the PON1 polymorphisms significantly affected serum lipid, lipoprotein or apolipoprotein concentrations. Our findings suggest that the physiological relevance of the PON1 polymorphisms is that they are associated with significant differences in serum PON1 activity, and the impact of PON1 polymorphisms on this activity is substrate-dependent.

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“…Our findings are consistent with the study conducted by Mackness et al (2000) which demonstrated a graded risk relation between presence, as well as severity, of DR and PON1 R allele. 30 In the majority of studies, persons with PON1 R carriers were found to be at increased risk of microvascular and macrovascular complications. [31][32][33] However, Flekac et al (2008) compared diabetic patients with and without DR and found no difference in PON1 phenotype distribution in two groups.…”

Section: Discussionmentioning

confidence: 99%