rs7770370 — HLA-DPB1

Intronic tag SNP in HLA-DPB1 (and upstream of HLA-DPA1) that marks the HLA-DP haplotype controlling antigen-presenting cell surface expression; the G allele is strongly associated with chronic hepatitis B infection susceptibility and impaired hepatitis B vaccine antibody response across multiple populations

See your personal result for HLA-DPB1

Upload your DNA data to find out which genotype you carry and what it means for you.

Upload your DNA data

Works with 23andMe, AncestryDNA, and other DNA test exports. Results in under 60 seconds.

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 and marks a haplotype block that controls how efficiently the immune system presents HBV antigens. The G allele at this position tags a low-expression HLA-DP haplotype — carriers produce fewer HLA-DP antigen-presenting complexes, mount weaker T-cell responses to HBV, and face significantly higher odds of chronic infection and vaccine non-response.

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 — instead, it acts as a tag SNP33 tag SNP
A marker in strong linkage disequilibrium with the functional haplotype; it doesn't cause the effect itself but reliably identifies carriers of the causally relevant low-expression haplotype for a haplotype including the eQTL variants rs3077 (HLA-DPA1 3′ UTR) and rs9277535 (HLA-DPB1 3′ UTR), both of which directly reduce HLA-DP mRNA expression. The G allele at rs7770370 co-segregates with the G allele at rs3077 and the A allele at rs9277535 — the combination associated with the lowest HLA-DPA1 and HLA-DPB1 surface density on liver antigen-presenting cells. With fewer HLA-DP molecules available, HBV peptide display to CD4+ T cells is impaired, T-helper activation is blunted, antibody production against the HBV surface antigen (anti-HBs) is reduced, and cytotoxic T-cell killing of infected hepatocytes is diminished.

The Evidence

Wu et al. (2015)44 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)55 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)66 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)77 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 association is present across Asian, European, and mixed-ancestry cohorts, though 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.

For those already identified with chronic HBV infection, the HLA-DP haplotype also predicts treatment response dynamics — AA haplotype carriers have better HBsAg seroclearance during nucleot(s)ide analogue therapy, making genotype relevant to hepatologist treatment planning.

Interactions

rs7770370 is part of the same HLA-DP haplotype block as rs3077 (HLA-DPA1 3′ UTR) and rs9277535 (HLA-DPB1 3′ UTR). These three variants tag a low-expression haplotype that produces reduced HLA-DPA1 and HLA-DPB1 mRNA. The combined protective haplotype (A allele at rs3077 and A allele at rs9277535) shows a stronger additive protective effect against chronic HBV (OR 0.57 in Indonesian replication, CI 0.36–0.92) than either variant alone. Profiling all three SNPs together provides the most complete picture of HLA-DP expression and HBV susceptibility in a given individual. Each additional G allele across this haplotype incrementally reduces HLA-DP surface density and immune clearance capacity.

Genotype Interpretations

What each possible genotype means for this variant.

AA HLA-DP Protective Haplotype Normal

Protective HLA-DPB1 genotype — strong HBV antigen presentation

The AA genotype tags the high-expression HLA-DP haplotype via its co-segregation with the protective A alleles at rs3077 (HLA-DPA1 3′ UTR eQTL) and rs9277535 (HLA-DPB1 3′ UTR eQTL). Higher HLA-DPA1 and HLA-DPB1 mRNA expression means more surface HLA-DP complexes on antigen-presenting cells — more HBV peptides displayed to CD4+ T helper cells, stronger adaptive immunity coordination, and more efficient anti-HBs antibody production after vaccination. 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

One G allele means one copy of the low-expression HLA-DP haplotype and one copy of the high-expression haplotype. The additive effect produces intermediate HLA-DP surface density — enough for most individuals to mount adequate vaccine responses, but with an increased minority who generate suboptimal anti-HBs levels. 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 GG genotype carries two copies of the low-expression HLA-DP haplotype, maximally suppressing HLA-DPA1 and HLA-DPB1 surface density on antigen-presenting cells. This reduces peptide display to CD4+ T helper cells, blunts antibody production, and diminishes cytotoxic T-cell responses against HBV-infected hepatocytes. 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. If already chronically infected with HBV, GG carriers may respond less robustly to nucleot(s)ide analogue therapy and benefit from close virological monitoring and hepatologist-led treatment optimisation.