Correlation Between Serum PON1 Arylesterase Activity and Rs 854573 PON1 A Polymorphism with Type 2 Diabetes in an Eastern Indian Cohort

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder of glucose and lipids and characterized by defect in insulin secretion or action. Oxidative imbalance has also been implicated in the etiology of diabetes. Paraoxonase-1 (PON1) is an esterase and lactonase which is found in the circulation bound to high-density lipoproteins (HDL). Alterations and associations of circulating PON1 levels with a variety of diseases including diabetes encourages us to investigate the possible association between PON1 A/G rs854573 polymorphism and serum PON1 activity with T2DM. The study essentially follows a population based case-control format with 101 diabetic and 102 healthy controls. The findings revealed association of polymorphism with the diseased status (p value 0.0002, OR 3.49, 95% CI 1.77 to 6.9). With significantly higher range of mean serum PON1 Arylesterase (AREase) activity in control (9.99 – 0.96 kU/L) than in diabetic patients (5.25 - 0.508 kU/L) (p value,<0.001), a large difference between common diabetic AA genotype and combined diabetic heterozygous and homozygous genotypes (AG+GG) for risk allele G (assymptometic p value,<0.001), or in between two AA genotypes (Diabetic/Non diabetic, p<0.001), was explored by parametric and non parametric statistical pairwise comparison. Serum PON1 activity was found to be independent of other clinical factors such as plasma glucose levels. Western blot analysis of serum samples detected a significant difference of PON1 proteins in diabetic patients and control subjects (p value 0.008). In conclusion serum PON1 AREase activity which to an extent correlated with PON1 promoter polymorphism might be a good predictor of the disease risk.