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Relationship of p22phox C242T polymorphism with nephropathy in type 2 diabetic patients
Kátia G Santos1, Luís H Canani, Jorge L Gross
1Genetics Department, Federal University of Rio Grande do Sul, Porto Alegre, RS - Brazil.
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.
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