Strong influence of human leukocyte antigen (HLA)-DP gene variants on development of persistent chronic hepatitis B virus carriers in the han Chinese population

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Hepatology. 2010 Oct 20. [Epub ahead of print]

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.

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 2010).

PMID: 21207448 [PubMed - as supplied by publisher]