BACKGROUND & AIMS: Previously identified clinical risk factors such as sex, alcohol consumption, and age at infection do not accurately predict which patients with chronic hepatitis C (CHC) will develop advanced fibrosis (bridging fibrosis and cirrhosis). The aim of this study was to identify genetic polymorphisms that can predict the risk of advanced fibrosis in patients with CHC. METHODS: A total of 916 subjects with CHC was enrolled from 2 centers. A gene-centric disease association study of 24,832 putative functional, single nucleotide polymorphisms (SNPs) was performed. Of the 1609 SNPs that were significantly associated (P </= .05) with advanced fibrosis in the discovery cohort (University of California San Francisco [UCSF], N = 433), the first batch of 100 SNPs were selected for validation in the replication cohort (Virginia Commonwealth University [VCU], N = 483). RESULTS: A missense SNP in the DEAD box polypeptide 5 (DDX5) gene was significantly associated with an increased risk of advanced fibrosis in both the UCSF and the VCU cohorts (OR, 1.8 and 2.2, respectively). Two diplotype groups, carrying the haplotypes composed of the DDX5 SNP and 2 neighboring POLG2 SNPs were also significantly associated with an increased risk of advanced fibrosis and had comparable or better risk estimates. In addition, a missense SNP in the carnitine palmitoyltransferase 1A (CPT1A) gene was associated with a decreased risk of advanced fibrosis in both the UCSF and the VCU cohorts (OR, 0.3 and 0.6, respectively). CONCLUSIONS: Subjects with CHC carrying DDX5 minor allele or DDX5-POLG2 haplotypes are at an increased risk of developing advanced fibrosis, whereas those carrying the CPT1A minor allele are at a decreased risk.
BACKGROUND & AIMS: Previously identified clinical risk factors such as sex, alcohol consumption, and age at infection do not accurately predict which patients with chronic hepatitis C (CHC) will develop advanced fibrosis (bridging fibrosis and cirrhosis). The aim of this study was to identify genetic polymorphisms that can predict the risk of advanced fibrosis in patients with CHC. METHODS: A total of 916 subjects with CHC was enrolled from 2 centers. A gene-centric disease association study of 24,832 putative functional, single nucleotide polymorphisms (SNPs) was performed. Of the 1609 SNPs that were significantly associated (P </= .05) with advanced fibrosis in the discovery cohort (University of California San Francisco [UCSF], N = 433), the first batch of 100 SNPs were selected for validation in the replication cohort (Virginia Commonwealth University [VCU], N = 483). RESULTS: A missense SNP in the DEAD box polypeptide 5 (DDX5) gene was significantly associated with an increased risk of advanced fibrosis in both the UCSF and the VCU cohorts (OR, 1.8 and 2.2, respectively). Two diplotype groups, carrying the haplotypes composed of the DDX5 SNP and 2 neighboring POLG2 SNPs were also significantly associated with an increased risk of advanced fibrosis and had comparable or better risk estimates. In addition, a missense SNP in the carnitine palmitoyltransferase 1A (CPT1A) gene was associated with a decreased risk of advanced fibrosis in both the UCSF and the VCU cohorts (OR, 0.3 and 0.6, respectively). CONCLUSIONS: Subjects with CHC carrying DDX5 minor allele or DDX5-POLG2 haplotypes are at an increased risk of developing advanced fibrosis, whereas those carrying the CPT1A minor allele are at a decreased risk.
Authors: Stephen F Kingsmore; Ingrid E Lindquist; Joann Mudge; Damian D Gessler; William D Beavis Journal: Nat Rev Drug Discov Date: 2008-03 Impact factor: 84.694
Authors: Marcin Krawczyk; Roman Müllenbach; Susanne N Weber; Vincent Zimmer; Frank Lammert Journal: Nat Rev Gastroenterol Hepatol Date: 2010-11-02 Impact factor: 46.802
Authors: Jennifer E Layden; Bamidele O Tayo; Scott J Cotler; Nina M Clark; Kristine Baraoidan; Scott L Friedman; Richard S Cooper Journal: Transplantation Date: 2014-05-27 Impact factor: 4.939
Authors: Etienne Patin; Zoltán Kutalik; Julien Guergnon; Stéphanie Bibert; Bertrand Nalpas; Emmanuelle Jouanguy; Mona Munteanu; Laurence Bousquet; Laurent Argiro; Philippe Halfon; Anne Boland; Beat Müllhaupt; David Semela; Jean-François Dufour; Markus H Heim; Darius Moradpour; Andreas Cerny; Raffaele Malinverni; Hans Hirsch; Gladys Martinetti; Vijayaprakash Suppiah; Graeme Stewart; David R Booth; Jacob George; Jean-Laurent Casanova; Christian Bréchot; Charles M Rice; Andrew H Talal; Ira M Jacobson; Marc Bourlière; Ioannis Theodorou; Thierry Poynard; Francesco Negro; Stanislas Pol; Pierre-Yves Bochud; Laurent Abel Journal: Gastroenterology Date: 2012-07-27 Impact factor: 22.682