Non-invasive screening of HLA-DPA1 and HLA-DPB1 alleles for persistent hepatitis B virus infection: susceptibility for vertical transmission and toward a personalized approach for vaccination and treatment

Abstract

Background: Polymorphisms in the major histocompatibility complex (MHC) and non-MHC genes were recently reported to be associated with persistent hepatitis B virus (HBV) infection and host response to hepatitis B vaccine in Asian populations. We aimed to confirm the associations in Chinese population and develop a non-invasive screening method for the risk loci.

Methods: We genotyped 2 risk alleles on the MHC loci, HLA-DPA1 (rs3077) and HLA-DPB1 (rs9277535), and 1 risk allele near a non-MHC gene, FOXP1 (rs6789153) using high-resolution melting curve analysis. With minimal processing steps and time, salivary DNA was extracted with a modified protocol of a blood kit. We compared the genotyping fidelity between peripheral blood DNA and salivary DNA.

Results: Both rs3077 and rs9277535, but not rs6789153, are significantly associated with CHB in Chinese population (p-value<0.001). High genotype concordance between different sources of genomic DNA was obtained.

Conclusions: Genotyping salivary DNA using our modified methods provides a non-invasive fast screening for host susceptibility loci. The transmission mechanism of hepatitis B can now be modified by adding genetic susceptibility to the traditional vertical transmission model of hepatitis B.