Paraoxonase 1 ¹⁹²Gln/Arg polymorphism is associated with the risk of microangiopathy in Type 2 diabetes mellitus

AIMS: To investigate possible associations between diabetic microangiopathy and genetic polymorphisms in factors relevant to arterial thrombosis. METHODS: We conducted a case-control study on a total of 280 patients with Type 2 diabetes, comparing those without retinopathy or nephropathy (n = 92) and those with microangiopathies (n = 188), for the association of polymorphisms in four candidate genes, paraoxonase 1 (PON1), plasminogen activator inhibitor-1, fibrinogen, and platelet glycoprotein Ibalpha. RESULTS: There were no differences between the two study groups in gender distribution, age at diagnosis of diabetes (47.9 +/- 8.4 and 49.0 +/- 11.4 years, respectively), or duration of diabetes (14.9 +/- 4.5 and 14.5 +/- 8.4 years, respectively). Among the gene polymorphisms tested, the 192Gln/Arg polymorphism of PON1 was associated with the prevalence of retinopathy [odds ratio (OR) = 3.13, 95% confidence interval (CI) = 1.42-6.89, P = 0.0046, Gln/Gln vs. Gln/Arg and Arg/Arg]. This polymorphism was also associated with nephropathy (OR = 3.01, 95% CI = 1.30-6.98, P = 0.0103). There were no differences between the three PON1 genotypes (Gln/Gln, Gln/Arg, and Arg/Arg) with regard to the present disease status. Logistic regression analysis for the adjustment of other risk factors revealed that genotypes with PON1 192Arg were an independent predictor of retinopathy. No associations were found between microangiopathies and the other polymorphisms evaluated (plasminogen activator inhibitor-1, fibrinogen, and platelet glycoprotein Ibalpha). CONCLUSIONS: This study suggests that the presence of the 192Arg-allele in the PON1 gene is a genetic risk factor for microangiopathy in Type 2 diabetes mellitus.