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Association between PON 1 polymorphisms, PON activity and diabetes complications
Sabine E Hofer1, Bruce Bennetts, Albert K Chan
1Department of Endocrinology, The Children's Hospital at Westmead and University of Sydney, Sydney, Australia. sabine.e.hofer@uibk.ac.at <sabine.e.hofer@uibk.ac.at>
Journal of Diabetes and Its Complications
|September 5, 2006
Summary
Paraoxonase (PON) 1 gene variations impact enzyme activity and influence microvascular complications in type 1 diabetes. Specific genotypes are linked to increased urinary albumin loss or protection against retinopathy.
Area of Science:
- Genetics
- Molecular Biology
- Endocrinology
Background:
- The paraoxonase (PON) gene cluster on chromosome 7q21-22 encodes an enzyme crucial for protecting lipoproteins from oxidation.
- Lipid oxidation is implicated in the pathogenesis of vascular complications, and paraoxonase activity is often reduced in diabetic patients.
- Genetic variations within the PON 1 gene, particularly in promoter regions, are known to affect enzyme activity levels.
Purpose of the Study:
- To investigate the hypothesis that PON 1 genotypes influence paraoxonase activity and modulate the risk of microvascular disease in adolescents with type 1 diabetes.
- To identify specific PON 1 polymorphisms associated with paraoxonase and arylesterase activities and their correlation with diabetes complication status.
Main Methods:
- Genotyping of 156 Caucasian adolescents with type 1 diabetes for seven PON 1 polymorphisms, including a novel promoter polymorphism A(-1074)G.
- Analysis of the relationship between PON 1 genotypes, paraoxonase and arylesterase activities, and the presence of diabetes complications (e.g., retinopathy, nephropathy).
- Assessment of linkage disequilibrium among PON 1 promoter polymorphisms.
Main Results:
- Strong linkage disequilibrium was observed between PON 1 promoter polymorphisms.
- Both promoter and coding region polymorphisms significantly influenced paraoxonase and arylesterase activity levels.
- Specific genotypes (Leu/Leu 54, AA(-162), and GG(-1074)) were associated with increased urinary albumin excretion, indicating nephropathy risk.
- The GG(-907) genotype demonstrated a protective effect against diabetic retinopathy.
Conclusions:
- PON 1 gene polymorphisms significantly affect paraoxonase activity and are associated with microvascular complications in type 1 diabetes.
- Certain PON 1 genotypes may serve as predictive markers for the risk of developing specific diabetic complications, such as nephropathy and retinopathy.
- These findings highlight the role of genetic factors in the heterogeneity of diabetic vascular disease and suggest potential targets for risk stratification.
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