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Thématique :
- Foie
Originalité :
Très original
Solidité :
Intermédiaire
Doit faire évoluer notre pratique :
Pas encore
 
 
Nom du veilleur :
Docteur Bertrand HANSLIK
Coup de coeur :
 
 
Gut
  2018/08  
 
  2018 Aug;67(8):1517-1524.  
  doi: 10.1136/gutjnl-2016-313598.  
 
  Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis.  
 
  Alberts R, de Vries EMG, Goode EC, Jiang X, Sampaziotis F, Rombouts K, Böttcher K, Folseraas T, Weismüller TJ, Mason AL, Wang W, Alexander G, Alvaro D, Bergquist A, Björkström NK, Beuers U, Björnsson E, Boberg KM, Bowlus CL, Bragazzi MC, Carbone M, Chazouillères O, Cheung A, Dalekos G, Eaton J, Eksteen B, Ellinghaus D, Färkkilä M, Festen EAM, Floreani A, Franceschet I, Gotthardt DN, Hirschfield GM, Hoek BV, Holm K, Hohenester S, Hov JR, Imhann F, Invernizzi P, Juran BD, Lenzen H, Lieb W, Liu JZ, Marschall HU, Marzioni M, Melum E, Milkiewicz P, Müller T, Pares A, Rupp C, Rust C, Sandford RN, Schramm C, Schreiber S, Schrumpf E, Silverberg MS, Srivastava B, Sterneck M, Teufel A, Vallier L, Verheij J, Vila AV, Vries B, Zachou K; International PSC Study Group, The UK PSC Consortium, Chapman RW, Manns MP, Pinzani M, Rushbrook SM, Lazaridis KN, Franke A, Anderson CA, Karlsen TH, Ponsioen CY, Weersma RK  
  https://www.ncbi.nlm.nih.gov/pubmed/28779025  
 
 

Abstract

 

OBJECTIVE:

Primary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications.

DESIGN:

We collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients-obtained using the Illumina immunochip-with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes.

RESULTS:

We identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07×10-9). Kaplan-Meier survival analysis showed a 50.9% (95% CI 41.5% to 59.5%) transplant-free survival for homozygous AA allele carriers of rs853974 compared with 72.8% (95% CI 69.6% to 75.7%) for GG carriers at 10 years after PSC diagnosis. For the candidate gene in the region, RSPO3, we demonstrated expression in key liver-resident effector cells, such as human and murine cholangiocytes and human hepatic stellate cells.

CONCLUSION:

We present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene RSPO3 in key liver-resident effector cells. This warrants further assessments of the role of this potential key PSC modifier gene.

 
Question posée
 
Recherche de polymorphismes génétiques associés au risque d’évolution sévère et de complications des CSP.
 
Question posée
 
Un polymorphisme associé à une meilleure survie sans transplantation à été identifié, situé près du gène RSOP3, exprimé dans les cholangiocytes et les cellules étoilées du foie. Des loci associés au risque de cholangio-carcinome ont également été mis en évidence.
 
Commentaires

Travail d’envergure, à partir d’une cohorte internationale de 3400 patients.

 
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