Haplotype analysis of NAD(P)H oxidase p22 phox polymorphisms in end-stage renal disease.
NAD(P)H oxidase is one of the most important sources of reactive oxygen species and has been demonstrated to be upregulated by angiotensin II in the kidney. Given the effect of angiotensin-converting enzyme inhibitors on the progression of both diabetic and non-diabetic renal disease, we hypothesized that the polymorphisms of NAD(P)H oxidase are associated with development of end-stage renal disease (ESRD). We examined five polymorphisms in the CYBA gene encoding the p22 phox component of NAD(P)H oxidase, including 242C/T and 640A/G polymorphisms in 467 ESRD patients and 490 healthy individuals. The T allele of the 242C/T polymorphism showed a protective effect against ESRD only in the nondiabetic (non-DM) group (P = 0.0095), and haplotype estimation revealed that the frequency of 242C-640A was higher in the non-DM group (46.7%) than in the control group (39.7%). The CC-AA genotype was still significantly associated with ESRD without diabetes after adjusting for confounding factors (P = 0.035). In contrast, there was no difference between the DM group and the control group. In conclusion, we identified a risk haplotype for nondiabetic ESRD in the CYBA gene using haplotype analysis. Haplotype analysis proved useful for elucidating the genetic contribution of NAD(P)H oxidase p22 phox to ESRD.
Doi
Kent
K
Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
Noiri
Eisei
E
Nakao
Akihide
A
Fujita
Toshiro
T
Kobayashi
Shuzo
S
Tokunaga
Katsushi
K
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D017422:Sequence Analysis, DNA
D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D019255:NADPH Oxidases; C086986:CYBA protein, human