COVID-19 researchGene: HLA-DRB1
HLA-DRB1 was identified through an OMIM search for potential viral susceptibility genes. Initial triage by Illumina (Alison Coffey and team) was given a Tier 3 grouping (experimental evidence and association data consistent with viral susceptibility)
Created: 11 Jun 2020, 6:10 p.m. | Last Modified: 11 Jun 2020, 6:10 p.m.
Panel Version: 1.10
Non-Mendelian contribution of allelic variants to disease risk anticipated
Created: 1 May 2020, 10:22 a.m. | Last Modified: 1 May 2020, 10:22 a.m.
Panel Version: 0.171
Mode of inheritance
Comment on list classification: Rating as Green due to expert review and publications associated with HLA-DRB1 and viral susceptibility
Created: 22 Apr 2020, 4:47 p.m. | Last Modified: 22 Apr 2020, 4:47 p.m.
Panel Version: 0.137
Association of human leukocyte antigen class II alleles with severe acute respiratory syndrome in the Vietnamese population PMID: 19445991,
HLA-DRB1*12 was more frequently shown in SARS patients than in controls (corrected p = 0.042). HLA-DRB1*1202, the predominant allele in the Vietnamese population showed the strongest association with SARS in a dominant model (corrected p = 0.0065 and 0.0052, depending on the controls to be compared). Our results and accumulated data on HLA in the Asian populations would help in the understanding of associations with emerging infectious diseases.
Amino Acid Variation in HLA Class II Proteins Is a Major Determinant of Humoral Response to Common Viruses PMID: 26456283
The magnitude of the human antibody response to viral antigens is highly variable. To explore the human genetic contribution to this variability, we performed genome-wide association studies of the immunoglobulin G response to 14 pathogenic viruses in 2,363 immunocompetent adults. Significant associations were observed in the major histocompatibility complex region on chromosome 6 for influenza A virus, Epstein-Barr virus, JC polyomavirus, and Merkel cell polyomavirus. Using local imputation and fine mapping, we identified specific amino acid residues in human leucocyte antigen (HLA) class II proteins as the most probable causal variants underlying these association signals. Common HLA-DRβ1 haplotypes showed virus-specific patterns of humoral-response regulation
Clear and Independent Associations of Several HLA-DRB1 Alleles With Differential Antibody Responses to Hepatitis B Vaccination in Youth
To confirm and refine associations of human leukocyte antigen (HLA) genotypes with variable antibody (Ab) responses to hepatitis B vaccination, we have analyzed 255 HIV-1 seropositive (HIV(+)) youth and 80 HIV-1 seronegatives (HIV(-)) enrolled into prospective studies. In univariate analyses that focused on HLA-DRB1, -DQA1, and -DQB1 alleles and haplotypes, the DRB1*03 allele group and DRB1*0701 were negatively associated with the responder phenotype (serum Ab concentration > or = 10 mIU/mL) (P = 0.026 and 0.043, respectively). Collectively, DRB1*03 and DRB1*0701 were found in 42 (53.8%) out of 78 non-responders (serum Ab <10 mIU/mL), 65 (40.6%) out of 160 medium responders (serum Ab 10-1,000 mIU/mL), and 27 (27.8%) out of 97 high responders (serum Ab >1,000 mIU/mL) (P < 0.001 for trend). Meanwhile, DRB1*08 was positively associated with the responder phenotype (P = 0.010), mostly due to DRB1*0804 (P = 0.008).
Influence of HLA Supertypes on Susceptibility and Resistance to Human Immunodeficiency Virus Type 1 Infection
To determine whether HLA polymorphism influences HIV-1 susceptibility, a longitudinal cohort of highly HIV-1-exposed female sex workers based in Nairobi, Kenya, was prospectively analyzed. Decreased HIV-1 infection risk was strongly associated with possession of a cluster of closely related HLA alleles (A2/6802 supertype; incidence rate ratio [IRR], 0.45; 95% confidence interval [CI], 0.27-0.72; P=.0003). The alleles in this supertype are known in some cases to present the same peptide epitopes for T cell recognition. In addition, resistance to HIV-1 infection was independently associated with HLA DRB1*01 (IRR, 0.22; 95% CI, 0.06-0.60; P=.0003), which suggests that anti-HIV-1 class II restricted CD4 effector mechanisms may play an important role in protecting against viral challenge
Created: 11 Apr 2020, 12:05 p.m.
Mode of inheritance
Mode of pathogenicity
Publications for gene: HLA-DRB1 were set to PMID: 19445991,26456283,19597844,10823757,
Gene: hla-drb1 has been classified as Green List (High Evidence).
gene: HLA-DRB1 was added gene: HLA-DRB1 was added to Viral susceptibility. Sources: Literature Mode of inheritance for gene: HLA-DRB1 was set to Unknown Publications for gene: HLA-DRB1 were set to PMID: 19445991,26456283,19597844,10823757, Penetrance for gene: HLA-DRB1 were set to unknown Mode of pathogenicity for gene: HLA-DRB1 was set to Other Review for gene: HLA-DRB1 was set to GREEN