title: Haplotype analysis of NAD(P)H oxidase p22 phox polymorphisms in end-stage renal disease.
abstract: 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.
authors.affiliation: Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
authors.forename: Kent
authors.initials: K
authors.lastname: Doi
authors.forename: Eisei
authors.initials: E
authors.lastname: Noiri
authors.forename: Akihide
authors.initials: A
authors.lastname: Nakao
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
authors.forename: Shuzo
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
mesh_terms: 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
chemical_list: D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D019255:NADPH Oxidases; C086986:CYBA protein, human