Paraoxonase2 polymorphisms are associated with nephropathy in Type II diabetes

Aims/hypothesis. Paraoxonase is a member of a multigene family of three gen es. Paraoxonase2 gene polymorphisms have been associated with coronary hear t disease in non-diabetic patients and with an increased fasting glycaemia in patients with Type II (non-insulin-dependent) diabetes mellitus. We test ed the hypothesis of whether paraoxonase1 and paraoxonase2 polymorphisms we re associated with diabetic nephropathy. Methods. Our case-control study of 299 Swiss patients with Type TI diabetes included 147 patients with confirmed diabetic nephropathy. Results. In univariate analyses the two paraoxonase2 polymorphisms were ass ociated with diabetic nephropathy. When subjected to multivariate analyses, both paraoxonase2 polymorphisms remained statistically associated with dia betic nephropathy independent of traditional risk factors (paraoxonase2-148 : OR = 2.53, p = 0.003; paraoxonase2-311: OR = 2.67, p = 0.002). In additio n, BMI interacted with paraoxonase2 polymorphisms as a risk factor of nephr opathy. Conclusions/interpretation. The paraoxonase2 gene polymorphisms were signif icantly associated with diabetic nephropathy independent of traditional ris k factors in Type II diabetic patients. The susceptibility to diabetic neph ropathy was intensified by the degree of obesity. Pathophysiological pathwa ys should be investigated and could be involved in insulin resistance or li pids metabolism or both.