PMID- 21346778
OWN - NLM
STAT- MEDLINE
DCOM- 20120127
LR  - 20240420
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Print)
IS  - 1466-4879 (Linking)
VI  - 12
IP  - 6
DP  - 2011 Sep
TI  - Risk alleles for chronic hepatitis B are associated with decreased mRNA 
      expression of HLA-DPA1 and HLA-DPB1 in normal human liver.
PG  - 428-33
LID - 10.1038/gene.2011.11 [doi]
AB  - A genome-wide association study identified single nucleotide polymorphisms (SNPs) 
      rs3077 and rs9277535 located in the 3' untranslated regions of human leukocyte 
      antigen (HLA) class II genes HLA-DPA1 and HLA-DPB1, respectively, as the 
      independent variants most strongly associated with chronic hepatitis B. We 
      examined whether these SNPs are associated with mRNA expression of HLA-DPA1 and 
      HLA-DPB1. We identified gene expression-associated SNPs (eSNPs) in normal liver 
      samples obtained from 651 individuals of European ancestry by integrating 
      genotype (~650 000 SNPs) and gene expression (>39 000 transcripts) data from each 
      sample. We used the Kruskal-Wallis test to determine associations between gene 
      expression and genotype. To confirm findings, we measured allelic expression 
      imbalance (AEI) of complementary DNA compared with DNA in liver specimens from 
      subjects who were heterozygous for rs3077 and rs9277535. On a genome-wide basis, 
      rs3077 was the SNP most strongly associated with HLA-DPA1 expression (p=10(-48)), 
      and rs9277535 was strongly associated with HLA-DPB1 expression (p=10(-15)). 
      Consistent with these gene expression associations, we observed AEI for both 
      rs3077 (p=3.0 x 10(-7); 17 samples) and rs9277535 (p=0.001; 17 samples). We 
      conclude that the variants previously associated with chronic hepatitis B are 
      also strongly associated with mRNA expression of HLA-DPA1 and HLA-DPB1, 
      suggesting that expression of these genes is important in control of HBV.
FAU - O'Brien, T R
AU  - O'Brien TR
AD  - Infections and Immunoepidemiology Branch, National Cancer Institute, National 
      Institutes of Health, Department of Health and Human Services, Bethesda, MD 
      20892, USA. obrient@mail.nih.gov
FAU - Kohaar, I
AU  - Kohaar I
FAU - Pfeiffer, R M
AU  - Pfeiffer RM
FAU - Maeder, D
AU  - Maeder D
FAU - Yeager, M
AU  - Yeager M
FAU - Schadt, E E
AU  - Schadt EE
FAU - Prokunina-Olsson, L
AU  - Prokunina-Olsson L
LA  - eng
GR  - ImNIH/Intramural NIH HHS/United States
GR  - HHSN261200800001C/RC/CCR NIH HHS/United States
GR  - HHSN261200800001E/CA/NCI NIH HHS/United States
GR  - HHSN267200700004C/DK/NIDDK NIH HHS/United States
GR  - HHSN267200700004G/LM/NLM NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20110224
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (3' Untranslated Regions)
RN  - 0 (HLA-DP alpha-Chains)
RN  - 0 (HLA-DP beta-Chains)
RN  - 0 (HLA-DPA1 antigen)
RN  - 0 (HLA-DPB1 antigen)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Alleles
MH  - Gene Expression
MH  - *Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - HLA-DP alpha-Chains/*genetics/immunology
MH  - HLA-DP beta-Chains/*genetics/immunology
MH  - Hepatitis B virus/immunology
MH  - Hepatitis B, Chronic/*genetics/*immunology
MH  - Humans
MH  - Liver/*immunology
MH  - Polymorphism, Single Nucleotide
MH  - RNA, Messenger/*biosynthesis
PMC - PMC3169805
EDAT- 2011/02/25 06:00
MHDA- 2012/01/28 06:00
CRDT- 2011/02/25 06:00
PHST- 2011/02/25 06:00 [entrez]
PHST- 2011/02/25 06:00 [pubmed]
PHST- 2012/01/28 06:00 [medline]
AID - gene201111 [pii]
AID - 10.1038/gene.2011.11 [doi]
PST - ppublish
SO  - Genes Immun. 2011 Sep;12(6):428-33. doi: 10.1038/gene.2011.11. Epub 2011 Feb 24.