title: Endothelial nitric oxide genotypes and haplotypes are not associated with end-stage renal disease.
abstract: The identification of genetic markers associated with chronic kidney disease (CKD) may help to predict its development. Because reduced nitric oxide (NO) bioavailability and endothelial dysfunction are involved in CKD, genetic polymorphisms in the gene encoding the enzyme involved in NO synthesis (endothelial NO synthase [eNos]) may affect the susceptibility to CKD and the development of end-stage renal disease (ESRD). We compared genotype and haplotype distributions of three relevant eNOS polymorphisms (T(-786)C in the promoter region, Glu298Asp in exon 7, and 4b/4a in intron 4) in 110 healthy control subjects and 127 ESRD patients. Genotypes for the T(-786)C and Glu298Asp polymorphisms were determined by TaqMan(®) Allele Discrimination assay and real-time polymerase chain reaction. Genotypes for the intron 4 polymorphism were determined by polymerase chain reaction and fragment separation by electrophoresis. The software program PHASE 2.1 was used to estimate the haplotypes frequencies. We considered significant a probability value of p < 0.05/number of haplotypes (p < 0.05/8 = 0.0063). We found no significant differences between groups with respect to age, ethnicity, and gender. CKD patients had higher blood pressure, total cholesterol, and creatinine levels than healthy control subjects (all p < 0.05). Genotype and allele distributions for the three eNOS polymorphisms were similar in both groups (p > 0.05). We found no significant differences in haplotype distribution between groups (p > 0.05). The lack of significant associations between eNOS polymorphisms and ESRD suggests that eNOS polymorphisms may not be relevant to the genetic component of CKD that leads to ESRD.
authors.affiliation: Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirao Preto, Brazil.
authors.forename: Bernardo P
authors.initials: BP
authors.lastname: Marson
authors.forename: Samantha
authors.initials: S
authors.lastname: Dickel
authors.forename: Marília H
authors.initials: MH
authors.lastname: Ishizawa
authors.forename: Ingrid F
authors.initials: IF
authors.lastname: Metzger
authors.forename: Tatiane
authors.initials: T
authors.lastname: Izidoro-Toledo
authors.forename: Bartira Ercília Pinheiro
authors.initials: BE
authors.lastname: da Costa
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Poli-de-Figueiredo
authors.forename: Jose E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007676:Kidney Failure, Chronic / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers; D052250:Nitric Oxide Synthase Type III