TY - JOUR
T1 - Identification of Two Gene Variants Associated With Risk of Advanced Fibrosis in Patients With Chronic Hepatitis C
AU - Huang, Hongjin
AU - Shiffman, Mitchell L.
AU - Cheung, Ramsey C.
AU - Layden, Thomas J.
AU - Friedman, Scott
AU - Abar, Olivia T.
AU - Yee, Linda
AU - Chokkalingam, Anand P.
AU - Schrodi, Steven J.
AU - Chan, Jason
AU - Catanese, Joseph J.
AU - Leong, Diane U.
AU - Ross, David
AU - Hu, Xiaolan
AU - Monto, Alexander
AU - McAllister, Linda B.
AU - Broder, Samuel
AU - White, Thomas
AU - Sninsky, John J.
AU - Wright, Teresa L.
N1 - Funding Information:
Supported by Celera Diagnostics.
PY - 2006/6
Y1 - 2006/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33646351020&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2006.02.032
DO - 10.1053/j.gastro.2006.02.032
M3 - Article
C2 - 16697732
AN - SCOPUS:33646351020
SN - 0016-5085
VL - 130
SP - 1679
EP - 1687
JO - Gastroenterology
JF - Gastroenterology
IS - 6
ER -