5 years ago

Role of HLA-DP and HLA-DQ on the clearance of hepatitis B virus and the risk of chronic infection in a multiethnic population

Fabiana Heinrich, Cecilia Vistarini, Leila Haddad, Alfredo Martínez, Leandro Burgos Pratx, Beatriz Ameigeiras, María Laura Hulaniuk, Horacio Salamone, Ezequiel Ridruejo, Miguel Charre Samman, Julieta Trinks, Masaya Sugiyama, Roberto J. Fernández, Sebastián Marciano, Jorgelina Blejer, Mariela Caputo, Gustavo Echenique, Claudia D'Amico, Omar Galdame, Diego Flichman, Félix Nuñez, Susana Ceballos, Daniel Corach, Takayo Tsuchiura, Amalia Rojas, Katsushi Tokunaga, Adrián Gadano, Carlos Remondegui, Masashi Mizokami, Sonia Bartoli, Nao Nishida, Silvia E. Frías
Background & Aims HBV infection exhibits geographical variation in its distribution in South America. While HBV rates are low in central Argentina, the north-western region exhibits intermediate HBV rates. Unfortunately, the reasons that could explain this difference are still unknown. Methods A total of 1440 Argentines were recruited and grouped into HBV patients, HBV-resolved individuals and healthy controls. Genetic ancestry was assessed by analysis of biparental lineages and ancestry autosomal typing. SNPs of HLA-DPA1 (rs3077), HLA-DPB1 (rs9277542), HLA-DQB1 (rs2856718) and HLA-DQB2 (rs7453920) were determined, and HBV genotyping was performed by phylogenetic analysis in HBV patients. Results Native American ancestry prevailed in the north-western region when compared with central Argentina (P<.0001). However, no differences were observed among the three groups of each region. The distribution of HBV genotypes revealed significant differences (P<.0001). Three SNPs (rs3077, rs9277542 and rs7453920) showed a significant association with protection against chronic HBV and viral clearance in both regions. The remaining SNP showed a significant association with susceptibility to chronic HBV. The frequency rates of rs3077-T, related to protection against chronic HBV and viral clearance, were lower in north-western Argentina when compared with central Argentina. The same uneven frequency rates were observed for SNP rs9277542. Conclusions This is the first study addressing the associations between the HLA-DP and HLA-DQ loci and the protection against chronic HBV and viral clearance in a multiethnic South American population. The uneven distribution of HLA-DP and HLA-DQ supports the HBV epidemiological differences observed in these two regions of Argentina with dissimilar ancestry genetic background.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/liv.13405

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