PMID- 16697732
OWN - NLM
STAT- MEDLINE
DCOM- 20060622
LR  - 20131121
IS  - 0016-5085 (Print)
IS  - 0016-5085 (Linking)
VI  - 130
IP  - 6
DP  - 2006 May
TI  - Identification of two gene variants associated with risk of advanced fibrosis in 
      patients with chronic hepatitis C.
PG  - 1679-87
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.
FAU - Huang, Hongjin
AU  - Huang H
AD  - Celera Diagnostics, Alameda, California, USA. 
      hongjin.huang@celera.diagnostics.com
FAU - Shiffman, Mitchell L
AU  - Shiffman ML
FAU - Cheung, Ramsey C
AU  - Cheung RC
FAU - Layden, Thomas J
AU  - Layden TJ
FAU - Friedman, Scott
AU  - Friedman S
FAU - Abar, Olivia T
AU  - Abar OT
FAU - Yee, Linda
AU  - Yee L
FAU - Chokkalingam, Anand P
AU  - Chokkalingam AP
FAU - Schrodi, Steven J
AU  - Schrodi SJ
FAU - Chan, Jason
AU  - Chan J
FAU - Catanese, Joseph J
AU  - Catanese JJ
FAU - Leong, Diane U
AU  - Leong DU
FAU - Ross, David
AU  - Ross D
FAU - Hu, Xiaolan
AU  - Hu X
FAU - Monto, Alexander
AU  - Monto A
FAU - McAllister, Linda B
AU  - McAllister LB
FAU - Broder, Samuel
AU  - Broder S
FAU - White, Thomas
AU  - White T
FAU - Sninsky, John J
AU  - Sninsky JJ
FAU - Wright, Teresa L
AU  - Wright TL
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20060306
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 3.6.1.- (Ddx5 protein, human)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
RN  - EC 3.6.4.13 (RNA Helicases)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Alleles
MH  - DEAD-box RNA Helicases
MH  - Disease Progression
MH  - Female
MH  - Gene Expression Regulation
MH  - *Genetic Predisposition to Disease
MH  - Haplotypes
MH  - Hepatitis C, Chronic/*genetics/*pathology
MH  - Heterozygote
MH  - Humans
MH  - Liver Cirrhosis/*genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Genetic
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Probability
MH  - Prognosis
MH  - Prospective Studies
MH  - Protein Kinases/*genetics
MH  - RNA Helicases/*genetics
MH  - Risk Assessment
MH  - Sensitivity and Specificity
MH  - Severity of Illness Index
EDAT- 2006/05/16 09:00
MHDA- 2006/06/23 09:00
CRDT- 2006/05/16 09:00
PHST- 2005/07/20 00:00 [received]
PHST- 2006/02/08 00:00 [accepted]
PHST- 2006/05/16 09:00 [pubmed]
PHST- 2006/06/23 09:00 [medline]
PHST- 2006/05/16 09:00 [entrez]
AID - S0016-5085(06)00388-X [pii]
AID - 10.1053/j.gastro.2006.02.032 [doi]
PST - ppublish
SO  - Gastroenterology. 2006 May;130(6):1679-87. doi: 10.1053/j.gastro.2006.02.032. 
      Epub 2006 Mar 6.