title: Association between genotype and phenotype in uromodulin-associated kidney disease.
abstract: OBJECTIVE
  Uromodulin-associated kidney disease (UAKD) is an autosomal dominant disease caused by uromodulin (UMOD) gene mutations. This study explored genotype-phenotype correlations by examining the relationship between the type of UMOD mutation and the age at onset of ESRD.
  
  
  METHODS
  Extensive bibliographic research was used to ascertain patient-level data of all patients with UAKD published up to October 2011. Data included sex; ages at onset of hyperuricemia, gout, and ESRD; and UMOD genotype. Kaplan-Meier analysis and Cox proportional hazards models fitted with shared gamma frailty terms to adjust for within-family correlations were used to model time to event.
  
  
  RESULTS
  Thirty-one peer-reviewed publications reporting on 202 patients from 74 families with 59 different UMOD mutations were included. Median ages at onset of hyperuricemia, gout, and ESRD were 24, 40, and 56 years, respectively. Men developed gout and ESRD significantly earlier than did women (age at ESRD was 50 years for men and 60 for women; P=0.04, shared frailty model). Median ages at ESRD development were lowest with Cys77Tyr (37.5 years) and highest with Gln316Pro (65.5 years) UMOD mutations. Onset of ESRD was significantly earlier with UMOD mutations located within the epidermal growth factor domains 2 and 3 (range, 45-52 years; P<0.01 and 0.04, respectively) compared with the cysteine-rich domains (range, 60-65 years; by shared frailty model).
  
  
  CONCLUSIONS
  The UMOD genotype is related to the clinical phenotype of UAKD. This finding may assist in counseling of patients.
authors.affiliation: Renal Research Institute, 207 East 94th Street, New York, NY 10128, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Moskowitz
authors.forename: Sian E
authors.initials: SE
authors.lastname: Piret
authors.forename: Karl
authors.initials: K
authors.lastname: Lhotta
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kitzler
authors.forename: Adam P
authors.initials: AP
authors.lastname: Tashman
authors.forename: Erin
authors.initials: E
authors.lastname: Velez
authors.forename: Rajesh V
authors.initials: RV
authors.lastname: Thakker
authors.forename: Peter
authors.initials: P
authors.lastname: Kotanko
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D058949:Uromodulin / Q000235:genetics*
chemical_list: D058949:Uromodulin