title: Effect of genotype on the severity and volume progression of polycystic liver disease in autosomal dominant polycystic kidney disease.
abstract: The autosomal dominant polycystic kidney disease (APDKD) genotype influences renal phenotype severity but its effect on polycystic liver disease (PLD) is unknown. Here we analyzed the influence of genotype on liver phenotype severity.
  
  
  
  Clinical data were retrieved from electronic records of patients who were mutation screened with the available liver imaging (n = 434). Liver volumes were measured by stereology (axial or coronal images) and adjusted to height (HtLV).
  
  
  
  Among the patients included, 221 (50.9%) had truncating PKD1 (PKD1-T), 141 (32.5%) nontruncating PKD1 (PKD1-NT) and 72 (16.6%) PKD2 mutations. Compared with PKD1-NT and PKD2, patients with PKD1-T had greater height-adjusted total kidney volumes (799 versus 610 and 549 mL/m; P < 0.001). HtLV was not different (1042, 1095 and 1058 mL/m; P = 0.64) between the three groups, but females had greater HtLVs compared with males (1114 versus 1015 mL/m; P < 0.001). Annualized median liver growth rates were 1.68, 1.5 and 1.24% for PKD1-T, PKD1-NT and PKD2 mutations, respectively (P = 0.49), and remained unaffected by the ADPKD genotype when adjusted for age, gender and baseline HtLV. Females <48 years of age had higher annualized growth rates compared with those who were older (2.65 versus 0.09%; P < 0.001). After age 48 years, 58% of females with severe PLD had regression of HtLV, while HtLV continued to increase in males.
  
  
  
  In contrast to the renal phenotype, the ADPKD genotype was not associated with the severity or growth rate of PLD in ADKPD patients. This finding, along with gender influence, indicates that modifiers beyond the disease gene significantly influence the liver phenotype.
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Fouad T
authors.initials: FT
authors.lastname: Chebib
authors.affiliation: Division of Nephrology, Kosin University College of Medicine, Busan, South Korea.
authors.forename: Yeonsoon
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Heyer
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Irazabal
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Marie C
authors.initials: MC
authors.lastname: Hogan
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Harris
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Vicente E
authors.initials: VE
authors.lastname: Torres
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Ziad M
authors.initials: ZM
authors.lastname: El-Zoghby
mesh_terms: D000328:Adult; D003560:Cysts / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging*; D008107:Liver Diseases / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009929:Organ Size; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications / Q000235:genetics*; D050396:TRPP Cation Channels / Q000235:genetics* / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D004247:DNA; D050396:TRPP Cation Channels
keywords: ADPKD; PLD; genotype–phenotype; polycystic liver