HLA ASSOCIATION WITH THE OUTCOME OF HBV INFECTION: POSSESSION OF SPECIFIC ALLELES AND THE LEVEL OF HETEROZYGOSITY OF AN INFECTED INDIVIDUAL MAKE DIFFERENCE.

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HLA ASSOCIATION WITH THE OUTCOME OF HBV INFECTION: POSSESSION OF SPECIFIC ALLELES AND THE LEVEL OF HETEROZYGOSITY OF AN INFECTED INDIVIDUAL MAKE DIFFERENCE.
K.W. Lee PhD ¹, J.Y. Cheong MD ², Y.S. Ju MD ¹, D.H. Oh MD ¹, K.B. Hahm MD ² and S.W. Cho MD ². ¹ Hallym Institute for Genome Application, Hallym University, Anyang, Kyungki-Do, Korea and ² Gastroenterology, Ajou University, Suwon, Kyungki-Do, Korea .

This study investigated the association of HLA class I and class II alleles with the outcome of infection by hepatitis B virus (HBV). All subjects (n = 464) included in this study were Korean including 80 individuals with spontaneous viral clearance and 384 with chronic infection. HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 allelic types were identified by direct DNA sequence analysis. Data obtained from each study group were compared and statistically analyzed. Several HLA alleles appeared to be associated with the outcome of HBV infection with statistical significance (p=0.002-0.043): six with viral clearance (DRB1*1302 etc); two with viral persistence; and two with protection from disease progression. Comparative analysis based on the relative number of HBV-associated alleles carried by an infected individual, suggested that both clearance- and persistence-associated alleles have additive effects on HBV infection. In addition, heterozygosity at 4 HLA loci (A, B, DRB1 and DQB1) was strongly associated with protection from disease progression among individuals with chronic infection. Likewise, higher level of HLA heterozygosity of an HBV infected individual appeared to be beneficial to preventing disease progression (p=0.0008 by Mantel-Haenszel trend test). Lastly, haplotype analysis implied the existence of a synergistic modifier between DQB1 and DPB1 genes. In conclusion, both HLA class I and class II alleles are associated with the outcome of HBV infection at two different levels: possession of specific HLA alleles (or haplotypes) and the level of HLA heterozygosity of each infected individual.