Paraoxonase2 polymorphisms are associated with nephropathy in Type II diabetes.
OBJECTIVE
Paraoxonase is a member of a multigene family of three genes. Paraoxonase2 gene polymorphisms have been associated with coronary heart disease in non-diabetic patients and with an increased fasting glycaemia in patients with Type II (non-insulin-dependent) diabetes mellitus. We tested the hypothesis of whether paraoxonase1 and paraoxonase2 polymorphisms were associated with diabetic nephropathy.


METHODS
Our case-control study of 299 Swiss patients with Type II diabetes included 147 patients with confirmed diabetic nephropathy.


RESULTS
In univariate analyses the two paraoxonase2 polymorphisms were associated with diabetic nephropathy. When subjected to multivariate analyses, both paraoxonase2 polymorphisms remained statistically associated with diabetic nephropathy independent of traditional risk factors (paraoxonase2-148: OR = 2.53, p = 0.003; paraoxonase2-311: OR = 2.67, p = 0.002). In addition, BMI interacted with paraoxonase2 polymorphisms as a risk factor of nephropathy.


CONCLUSIONS
The paraoxonase2 gene polymorphisms were significantly associated with diabetic nephropathy independent of traditional risk factors in Type II diabetic patients. The susceptibility to diabetic nephropathy was intensified by the degree of obesity. Pathophysiological pathways should be investigated and could be involved in insulin resistance or lipids metabolism or both.
Pinizzotto
M
M
Endocrinology and Diabetology Division, Lausanne, Switzerland.
Castillo
E
E
Fiaux
M
M
Temler
E
E
Gaillard
R C
RC
Ruiz
J
J
D043303:Aryldialkylphosphatase; D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000235:genetics*; D004950:Esterases / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human