PMID- 17935228
OWN - NLM
STAT- MEDLINE
DCOM- 20080110
LR  - 20140730
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Linking)
VI  - 46
IP  - 6
DP  - 2007 Dec
TI  - Evidence for human leukocyte antigen heterozygote advantage against hepatitis C 
      virus infection.
PG  - 1713-21
AB  - Outcomes of infection with hepatitis C virus (HCV) vary widely, from asymptomatic 
      clearance to chronic infection, leading to complications that include fibrosis, 
      cirrhosis, hepatocellular carcinoma, and liver failure. Previous studies have 
      reported statistical associations between human leukocyte antigen (HLA) 
      heterozygosity and favorable outcomes of infection with either hepatitis B virus 
      (HBV) or human immunodeficiency virus (HIV) (the "heterozygote advantage"). To 
      investigate whether HLA zygosity is associated with outcome of HCV infection, we 
      used data from the United States Organ Procurement and Transplantation Network 
      database of 52,435 liver transplant recipients from 1995 through 2005. Of these, 
      30,397 were excluded for lack of HLA data, retransplantation, known HIV 
      infection, or insufficient information regarding HBV infection. The remaining 
      cases were analyzed for associations between HCV infection and HLA zygosity with 
      1-sided Fisher's exact tests. Results show significantly lower proportions of 
      HLA-DRB1 heterozygosity among HCV-infected than uninfected cases. The differences 
      were more pronounced with alleles represented as functional supertypes (P = 1.05 
      x 10(-6)) than as low-resolution genotypes (P = 1.99 x 10(-3)). No significant 
      associations between zygosity and HCV infection were found for other HLA loci. 
      CONCLUSION: These findings constitute evidence for an advantage among carriers of 
      different supertype HLA-DRB1 alleles against HCV infection progression to 
      end-stage liver disease in a large-scale, long-term study population. Considering 
      HLA polymorphism in terms of supertype diversity is recommended in strategies to 
      design association studies for robust results across populations and in trials to 
      improve treatment options for patients with chronic viral infection. Access to 
      deidentified clinical information relating genetic variation to viral infection 
      improves understanding of variation in infection outcomes and might help to 
      personalize medicine with treatment options informed in part by human genetic 
      variation.
FAU - Hraber, Peter
AU  - Hraber P
AD  - Theoretical Biology & Biophysics, Los Alamos National Laboratory, Los Alamos, NM 
      87545, USA. phraber@lanl.gov
FAU - Kuiken, Carla
AU  - Kuiken C
FAU - Yusim, Karina
AU  - Yusim K
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Alleles
MH  - HLA Antigens/*genetics
MH  - Haplotypes
MH  - Hepatitis C/*genetics/immunology
MH  - Heterozygote
MH  - Humans
EDAT- 2007/10/16 09:00
MHDA- 2008/01/11 09:00
CRDT- 2007/10/16 09:00
PHST- 2007/10/16 09:00 [pubmed]
PHST- 2008/01/11 09:00 [medline]
PHST- 2007/10/16 09:00 [entrez]
AID - 10.1002/hep.21889 [doi]
PST - ppublish
SO  - Hepatology. 2007 Dec;46(6):1713-21. doi: 10.1002/hep.21889.