Polymorphisms of human paraoxonase 1 gene (PON1) and susceptibility to diabetic nephropathy in type I diabetes mellitus.
OBJECTIVE
Oxidative stress is a putative mechanism in the development of diabetic nephropathy. Paraoxonase gene 1 is an HDL-bound enzyme that protects tissues against oxidative damage. Three common polymorphisms of paraoxonase gene 1, T-107C in the promoter, Leu54Met and Gln192Arg, that modify paraoxonase activity have been associated with cardiovascular disease. This study aimed to find whether these polymorphisms also contribute to the development of diabetic nephropathy.


METHODS
The association between diabetic nephropathy and these three polymorphisms was examined in a case-control study. For this purpose, genomic DNA was collected from 188 patients with Type I (insulin-dependent) diabetes mellitus and diabetic nephropathy and from 179 unrelated patients with Type I diabetes but without diabetic nephropathy despite the duration of diabetes of 15 or more years.


RESULTS
The genotype and allele frequencies for each of the three polymorphisms (T-107C, Leu54Met and Gln192Arg) were similar in cases and control subjects.


CONCLUSIONS
The three polymorphisms in paraoxonase gene 1 that have been associated with serum levels of paraoxonase are not associated with diabetic nephropathy. We show that this genetically determined component of the antioxidant capacity of HDL does not play a critical part in the development of diabetic nephropathy.
Araki
S
S
Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA.
Makita
Y
Y
Canani
L
L
Ng
D
D
Warram
J H
JH
Krolewski
A S
AS
D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution; D043303:Aryldialkylphosphatase; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000235:genetics*; D004950:Esterases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012016:Reference Values
D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human