rs7770370 — HLA-DPB1

Intronic tag SNP in HLA-DPB1 (and upstream of HLA-DPA1); the G allele is strongly associated with chronic hepatitis B infection susceptibility and impaired hepatitis B vaccine antibody response across multiple populations

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HLA-DPB1 rs7770370 — A Gatekeeper Haplotype for Hepatitis B Immunity

When the hepatitis B virus enters the body, the immune system must decide within weeks whether to mount a clearing response or allow the infection to persist for life. That decision hinges heavily on HLA class II antigen presentation11 HLA class II antigen presentation
The process by which antigen-presenting cells — dendritic cells, macrophages, B cells — display viral peptide fragments on MHC class II molecules to CD4+ T helper cells, initiating adaptive immunity. rs7770370 sits within the HLA-DPB1 gene on chromosome 6p21.

The Mechanism

HLA-DP is a heterodimeric surface receptor composed of an alpha chain (HLA-DPA1) and a beta chain (HLA-DPB1), expressed on antigen-presenting cells including the Kupffer cells and dendritic cells of the liver. It binds viral peptide fragments in its groove and displays them to CD4+ T helper cells22 CD4+ T helper cells
The immune cells that coordinate both antibody production by B cells and activation of CD8+ cytotoxic T cells — the two arms of adaptive immunity needed to clear HBV. rs7770370 is an intronic variant in HLA-DPB1 that does not change the protein sequence.

The Evidence

Wu et al. (2015)33 Wu et al. (2015)
SNP rs7770370 in HLA-DPB1 loci as a major genetic determinant of response to booster hepatitis B vaccination. J Gastroenterol Hepatol performed the first GWAS specifically focused on rs7770370, studying 15- to 18-year-olds who had received primary HBV vaccination in infancy but failed to maintain protective antibody levels. Among HLA-DP candidate SNPs in a 47 kb block, rs7770370 was the sentinel signal: AA homozygotes had an adjusted odds ratio of just 0.095 (CI 0.030–0.307) for vaccine non-response relative to GG homozygotes — a greater than 10-fold difference — while AG heterozygotes showed a 2-fold advantage (OR 0.524). This quantified the G allele as the dominant genetic driver of long-term vaccine failure in this population.

Roh et al. (2016)44 Roh et al. (2016)
HLA-DP variants and hepatitis B vaccine responsiveness in Korean infants. Vaccine extended the finding to 290 infants (the primary vaccination setting), showing that the AA genotype was associated with vaccine response (relative risk 2.5, p=0.033) and with high-titer response specifically (RR 2.7, p<0.001). The A allele was significantly more frequent in responders (p<0.01), confirming the genotype predicts immunogenicity from the very first vaccination series.

For chronic HBV infection susceptibility, Huang et al. (2020)55 Huang et al. (2020)
Taiwan Biobank GWAS of 15,352 HBV-exposed participants. Aliment Pharmacol Ther identified rs7770370 as the single most significant HLA class II signal for HBV chronicity (P=2.73×10⁻³⁵, Pcorrected <8.6×10⁻⁸). The HLA-DPB1*05:01 allele — in strong LD with the G allele — conferred OR 1.61 (CI 1.29–2.01) for chronic HBV. In a Thai GWAS, Ashouri et al. (2022)66 Ashouri et al. (2022)
Genome-wide Association Study for Chronic Hepatitis B in the Thai Population. Front Genet independently replicated the association (p=7.71×10⁻¹⁰, OR=0.49 for the protective A allele). The G allele is far more common in populations with historically high HBV endemicity — about 46–54% in East Asians and Africans versus only 13% in Europeans — a pattern consistent with ongoing selection pressure from the virus.

Practical Actions

The key clinical implication is twofold: vaccine response and infection susceptibility. G-allele carriers — especially GG homozygotes — are at substantially higher risk of failing to develop protective antibodies after standard HBV vaccination, and of progressing to chronic infection if exposed. The appropriate actions are checking post-vaccination antibody titres and, for those with exposure risk, baseline serology and follow-up for signs of chronicity.

Genotype Interpretations

What each possible genotype means for this variant.

AA HLA-DP Protective Haplotype Normal

Protective HLA-DPB1 genotype — strong HBV antigen presentation

Standard three-dose hepatitis B vaccination typically achieves protective anti-HBs titres ≥10 mIU/mL in this genotype group at the expected population rate.

AG HLA-DP Intermediate Intermediate

One G allele — moderately elevated HBV susceptibility and reduced vaccine response

The Wu et al. GWAS (2015) found AG heterozygotes had adjusted OR 0.524 for vaccine non-response relative to GG — so they are better protected than GG carriers, but not as robustly as AA individuals. For those with occupational, household, or travel-related HBV exposure risk, post-vaccination titre confirmation adds a meaningful safety margin.

GG HLA-DP Risk Haplotype High Risk

Two G alleles — substantially elevated HBV susceptibility and high risk of vaccine non-response

The Wu et al. (2015) GWAS established that GG carriers were the reference group for the highest vaccine non-response, with AA individuals showing OR 0.095 — implying GG carriers have roughly 10× higher non-response odds relative to AA. The Huang et al. (2020) Taiwan Biobank study identified rs7770370 as the top HLA class II signal for HBV chronicity at P=2.73×10⁻³⁵, with the linked HLA-DPB1*05:01 haplotype conferring OR 1.61 for chronic infection. The Ashouri Thai GWAS independently replicated the signal at p=7.71×10⁻¹⁰.