Relationship of p22phox C242T polymorphism with nephropathy in type 2 diabetic patients.
BACKGROUND
In this case-control study, we investigated the possible involvement of the p22phox C242T polymorphism in the development and progression of diabetic nephropathy (DN) in 535 Caucasian Brazilians with type 2 diabetes. We also evaluated the effects of the interaction of the C242T polymorphism with smoking and hypercholesterolemia on the susceptibility to nephropathy.


METHODS
Genotype analysis was performed using polymerase chain reaction (PCR) followed by digestion with restriction enzyme. Logistic regression analysis was used to control for independent risk factors associated with nephropathy.


RESULTS
The genotype frequencies in patients with overt DN (CC/CT/TT: 0.36/0.47/0.17) were not significantly different from those of diabetic individuals with normoalbuminuria (0.47/0.41/0.12) or microalbuminuria (0.42/0.48/0.10) (p=0.214). Likewise, there were no differences in the T allele frequency among patients with normoalbuminuria, microalbuminuria or overt DN (0.33, 0.34 and 0.40, respectively; p=0.111). However, the T allele was found to be more frequent among smokers with overt nephropathy (macroalbuminuria and/or in dialysis) than those who had normoalbuminuria (43 vs. 32%, p=0.045). The multiple logistic regression analysis confirmed that the CT+TT genotypes were independently associated with a higher risk of having overt nephropathy among smokers [odds ratio (OR)=6.76, 95% confidence interval (95% CI) 1.83-25.02].


CONCLUSIONS
Our study shows a gene-environment interaction associated with the increased risk of DN progression in Caucasian Brazilian smokers with type 2 diabetes. Further studies should be performed to clarify whether it exists, and to what extent there is a relationship between the p22phox C242T polymorphism and DN.
Santos
Kátia G
KG
Genetics Department, Federal University of Rio Grande do Sul, Porto Alegre, RS - Brazil.
Canani
Luís H
LH
Gross
Jorge L
JL
Tschiedel
Balduíno
B
Souto
Kátia E
KE
Roisenberg
Israel
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000235:genetics; D003928:Diabetic Nephropathies / Q000097:blood / Q000209:etiology / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D019255:NADPH Oxidases / Q000097:blood / Q000235:genetics*; D010750:Phosphoproteins / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012307:Risk Factors
D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D004247:DNA; D019255:NADPH Oxidases; C086986:CYBA protein, human