标题: Strong influence of human leukocyte antigen (HLA)-DP gene variants on developmen [打印本页] 作者: StephenW 时间: 2011-2-8 22:25 标题: Strong influence of human leukocyte antigen (HLA)-DP gene variants on developmen
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Hepatology. 2011 Feb;53(2):422-8. doi: 10.1002/hep.24048. Epub 2011 Jan 4.
Strong influence of human leukocyte antigen (HLA)-DP gene variants on
development of persistent chronic hepatitis B virus carriers in the Han Chinese
population.
Guo X, Zhang Y, Li J, Ma J, Wei Z, Tan W, O'Brien SJ.
Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory
Medicine and Life Science, Wenzhou Medical College, Zhejiang, China; State Key
Laboratory for Infectious Diseases Prevention and Control, Institute for Viral
Disease Control and Prevention, Chinese Center for Disease Control and
Prevention, Beijing, China; Laboratory of Genomic Diversity, Center for Cancer
Research, National Cancer Institute, National Institutes of Health, Frederick,
MD. [email protected].
Abstract
Chronic hepatitis B virus (HBV) infection is a major health issue, especially in
Asia. A recent genome-wide association study (GWAS) implicated genetic variants
in the human leukocyte antigen (HLA)-DP locus associated with chronic hepatitis
B in Japanese and Thai populations. To confirm whether the polymorphisms at the
HLA-DP genes are associated with persistent chronic HBV infection in Han
Chinese, we conducted an independent case-control study using 521 persistent
chronic HBV carriers and 819 controls that included 571 persons with HBV natural
clearance and 248 never HBV-infected (healthy) individuals. Eleven single
nucleotide polymorphisms (SNPs) in a region including HLA-DPA and HLA-DPB and an
adjacent SNP in strong linkage disequilibrium (LD) with a neighboring HLA-DR13
locus were genotyped using the TaqMan SNP genotyping assay. Eleven variants at
HLA-DP showed a strong association with persistent chronic HBV carrier status (P
= 1.82 × 10(-12) to 0.01). We also stratified the analysis by HBV clearance
status to test the association between these polymorphisms and HBV natural
clearance; similar results were obtained (P = 2.70 × 10(-11) to 0.003).
Included SNPs define highly structured haplotypes that were also strongly
associated with HBV chronic infection (block 1: odds ratio [OR] = 0.54, P = 8.73
× 10(-7) ; block 2: OR = 1.98, P = 1.37 × 10(-10) ). These results further
confirm that genetic variants in the HLA-DP locus are strongly associated with
persistent HBV infection in the Han Chinese population. (HEPATOLOGY
2011;53:422-428).