title: The ENOS polymorphism is not associated with severity of renal disease in polycystic kidney disease 1.
abstract: BACKGROUND
  The renal phenotype in autosomal dominant polycystic kidney disease (ADPKD) is highly variable. Although genetic and allelic heterogeneity explain part of this variability, significant intrafamilial differences in time to end-stage renal disease (ESRD) indicate that genetic modifiers and the environment influence renal phenotype. Previously, a glutamic acid to aspartic acid polymorphism at residue 298 (E/D298) of the endothelial nitric oxide synthase (eNOS) gene ENOS was associated with disease severity in males with ADPKD.
  
  
  METHODS
  We typed the E/D298 polymorphism in 215 mutation-defined polycystic kidney disease 1 (PKD1) patients from 80 families. In this population, 96 patients had ESRD, with a median time to renal failure of 53 years.
  
  
  RESULTS
  Distribution of ENOS genotypes was 86 (40%), 106 (49.3%), and 23 (10.7%) for EE, ED, and DD, respectively. The occurrence of hypertension was not significantly different between genotypes. Kaplan-Meier renal survival analysis showed no significant difference between genotypes, with a median age to ESRD of 53 years for all genotypes in the total population and 52, 52, and 51 years (men) and 57, 53, and 55 years (women) for DD, DE, and EE, respectively.
  
  
  CONCLUSIONS
  Although the D298 ENOS allele may be associated with lower vascular activity of eNOS, this did not correlate with severity of renal disease in this PKD1 population. An important difference between this study and one finding a modifying role for ENOS was the rigor in defining the PKD1 population. This study shows the importance of using mutation-characterized populations for association studies in ADPKD.
authors.affiliation: Division of Nephrology and Section of Biostatistics, Mayo Clinic, Rochester, MN, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Walker
authors.forename: Mark
authors.initials: M
authors.lastname: Consugar
authors.forename: Jeff
authors.initials: J
authors.lastname: Slezak
authors.forename: Sandro
authors.initials: S
authors.lastname: Rossetti
authors.forename: Vicente E
authors.initials: VE
authors.lastname: Torres
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Winearls
authors.forename: Peter C
authors.initials: PC
authors.lastname: Harris
mesh_terms: D000367:Age Factors; D000483:Alleles; D015331:Cohort Studies; D005260:Female; D005828:Genetics, Population / Q000706:statistics & numerical data; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics; D007674:Kidney Diseases / Q000201:enzymology* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D016891:Polycystic Kidney, Autosomal Dominant / Q000201:enzymology* / Q000235:genetics* / Q000401:mortality; D011110:Polymorphism, Genetic / Q000235:genetics*; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III