Strong influence of human leukocyte antigen (HLA)-DP gene variants on developmen

StephenW

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).

Copyright © 2010 American Association for the Study of Liver Diseases.
PMID: 21274863 [PubMed - in process]

杂志。 2011年2月，53（2）:422 - 8。分类号：10.1002/hep.24048。 EPUB的2011年1月4日。

强烈的影响人类白细胞抗原（HLA）- DP的基因变异体
持续性慢性乙型肝炎病毒携带者发展的汉人
人口。

过十，张勇，李江，马瑾，魏震，谭瓦，奥布莱恩律政司司长。

浙江省医学遗传学重点实验室，实验学校
医学与生命科学学院，温州医学院，浙江，中国;国家重点
实验室传染病预防和控制，病毒研究所
疾病控制和预防，疾病控制中心和中国
预防，北京，中国;基因组多样性实验室，癌症中心
研究，美国国家癌症研究所，卫生部，国家弗雷德里克研究院
医学博士。 [email protected]。

摘要
慢性乙型肝炎病毒（HBV）感染是一个严重的健康问题，尤其是在
亚洲。最近的全基因组关联研究（GWAS）牵连的遗传变异
在人类白细胞抗原（HLA）- DP的位点与慢性肝炎
B在日本和泰国人群。多态性是否确认在
人类白细胞抗原- DP的基因与持续慢性HBV感染汉
中，我们进行了一次独立病例对照研究以521持久
慢性乙肝病毒携带者和819名对照组，其中包括571人的自然与HBV
清理和248从未HBV感染（健康）个人。十一单
核苷酸多态性（SNPs）在包括人类白细胞抗原-政治部和HLA - DPB的和地区
相邻的单核苷酸多态性强连锁不平衡（LD）与相邻的HLA - DR13
位点的基因使用的TaqMan SNP分型检测。在十变种
人类白细胞抗原- DP的表现出与慢性乙肝病毒携带状态持续强关联（P
= 1.82 × 10（-12）至0.01）。我们还通过分层分析病毒清除
状态，以测试它们之间的基因多态性与HBV自然协会
清除;获得了类似的结果（P值2.70 × 10（-11）〜0.003）。
高度结构化的定义包括单核苷酸多态性单倍型也强烈
慢性乙肝病毒感染相关（第1座：胜算比[OR] = 0.54，P值8.73
× 10（-7）;块2：或= 1.98，P值1.37 × 10（-10））。这些结果进一步
确认在HLA - DP的位点的基因变异是紧密联系在一起
HBV持续感染的汉族人口。 （肝病
2011; 53:422-428）。

版权©为2010年美国肝病研究协会。
结论：21274863 [PubMed的 - 过程]




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