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 Ibα. 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, Gin/Gin 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 Ibα). 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.