Relation between development of nephropathy and the p22phox C242T and receptor for advanced glycation end product G1704T gene polymorphisms in type 2 diabetic patients.
OBJECTIVE
The development of diabetic nephropathy is considered to be associated with oxidative stress. NADPH oxidase and the receptor for advanced glycation end products (RAGE) have attracted attention as mechanisms of generating oxidative stress. We studied the relation between the genotypes of the NADPH p22phox C242T and RAGE G1704T polymorphisms and the development of diabetic nephropathy in type 2 diabetic patients.


METHODS
Using a retrospective review of clinical data, we allocated 181 Japanese type 2 diabetic patients to one of two groups: patients without diabetic nephropathy (group N; n = 108) and patients developing diabetic nephropathy (group D; n = 73) for 10 years or more. The p22phox C242T and RAGE G1704T polymorphisms were examined by Taqman PCR methods.


RESULTS
The frequency of the p22phox CC genotype was significantly higher in group D than in group N (90 vs. 79%; P = 0.0427). The frequency of the RAGE GT + TT genotype was significantly higher in group D than in group N (26 vs. 13%; P = 0.0313). The frequency of the combination of p22phox CC and RAGE GT + TT genotypes was significantly higher in group D than in group N (22 vs. 8%; P = 0.0057). In multiple logistic regression analysis, systolic blood pressure, HbA(1c), triglycerides, and the combination of polymorphisms were shown to be independent variables.


CONCLUSIONS
These results suggest that assessment of the combination of NADPH p22phox C242T and RAGE G1704T polymorphisms may be useful in identifying the risk for developing diabetic nephropathy in type 2 diabetic patients.
Matsunaga-Irie
Seiko
S
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Maruyama
Taro
T
Yamamoto
Yukihiro
Y
Motohashi
Yoshiko
Y
Hirose
Hiroshi
H
Shimada
Akira
A
Murata
Mitsuru
M
Saruta
Takao
T
D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009252:NADPH Dehydrogenase / Q000235:genetics*; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000235:genetics*; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014280:Triglycerides; D002784:Cholesterol; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase