title: Comparison between siblings and twins supports a role for modifier genes in ADPKD.
abstract: BACKGROUND
  Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by intrafamilial variability in renal disease progression, which could result from a combination of environmental and genetic factors. Although a role for modifier genes has been evidenced in mouse models, direct evidence in ADPKD patients is lacking. The analysis of variability in affected siblings and monozygotic (MZ) twins would help evaluate the relative contribution of environment and genetic factors on renal disease progression in ADPKD.
  
  
  METHODS
  The difference in the age at end-stage renal disease (ESRD) and the intraclass correlation coefficient (ICC) were quantified in a large series of ADPKD siblings from western Europe and compared with the values obtained in a series of MZ ADPKD twins from the same geographic area.
  
  
  RESULTS
  Fifty-six sibships (including 129 patients) and nine pairs of MZ twins were included. The difference in the age at ESRD was significantly higher in siblings (6.9 +/- 6.0 years, range 2 months to 23 years) than in MZ twins (2.1 +/- 1.9 years, range 1 month to 6 years; P = 0.02). Furthermore, the intraclass correlation coefficient was significantly lower in siblings than in MZ twins (0.49 vs. 0.92, respectively; P = 0.003). The intrafamilial difference in the age at ESRD was not influenced by gender.
  
  
  CONCLUSIONS
  These data substantiate the existence of a large intrafamilial variability in renal disease progression in ADPKD siblings. The fact that the variability in siblings is in a significant excess of that found in MZ twins strongly suggests that modifier genes account for a significant part of this variability.
authors.affiliation: Division of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Persu
authors.forename: Michel
authors.initials: M
authors.lastname: Duyme
authors.forename: Yves
authors.initials: Y
authors.lastname: Pirson
authors.forename: Xosé M
authors.initials: XM
authors.lastname: Lens
authors.forename: Thierry
authors.initials: T
authors.lastname: Messiaen
authors.forename: Martijn H
authors.initials: MH
authors.lastname: Breuning
authors.forename: Dominique
authors.initials: D
authors.lastname: Chauveau
authors.forename: Micheline
authors.initials: M
authors.lastname: Levy
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Grünfeld
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
mesh_terms: D000328:Adult; D000367:Age Factors; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics* / Q000503:physiopathology*; D012737:Sex Factors; D035781:Siblings; D014430:Twins, Monozygotic