rs2395029

This is a regulatory variant in the HLA-B gene.

Key Literature Trait Associations

Abacavir Hypersensitivity

This variant tags HLA-B*57:01, which causes severe abacavir hypersensitivity reaction — a potentially fatal immune-mediated response involving fever, rash, and multi-organ damage that worsens with rechallenge. HLA-B*57:01 testing is MANDATORY before starting abacavir (HIV treatment) per FDA label and all major HIV treatment guidelines. This is one of the most successful pharmacogenomic interventions: pre-treatment screening has virtually eliminated abacavir hypersensitivity reactions in clinical practice.

Mather KJ et al. “Adiponectin, change in adiponectin, and progression to diabetes in the Diabetes Prevention Program.” Diabetes 57(4):980-986 (2008)

Allele G

OR 960.00

p 1.0e-50

Large GWAS

Abacavir Hypersensitivity (HLA-B*57:01 Tag)

rs2395029 in HCP5 is a validated tag SNP for HLA-B*57:01, the allele that causes abacavir hypersensitivity syndrome in HIV-positive patients. The G allele predicts HLA-B*57:01 carrier status with ~100% sensitivity and ~99.4% specificity in Europeans. FDA labelling recommends HLA-B*57:01 testing before prescribing abacavir. This tag SNP was validated in >1,100 HIV patients (Young et al. 2008). Performance may be reduced in non-European populations due to HCP5 copy number variation and differing LD patterns.

Colombo S et al. “The HCP5 single-nucleotide polymorphism: a simple screening tool for prediction of hypersensitivity reaction to abacavir.” The Journal of Infectious Diseases 198(6):864-867 (2008)

Allele G

OR —

p 1.0e-50

Large GWAS

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GWAS Catalog Trait Associations (3)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

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ClinVar annotation

Conflicting Classifications

2 submitters

Abacavir hypersensitivity; Autism spectrum disorder

View on ClinVar →

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Research that mentions this SNP (2)

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Identification of a susceptibility locus in STAT4 for Behçet's disease in Han Chinese in a genome‐wide association study

AssociationN=4,539Shengping Hou et al.(2012)· Arthritis & Rheumatism

This Immunochip-based genetic analysis of Behçet's disease in a Spanish population (278 cases, 1,517 controls; 130 cases, 605 controls in replication) identified HLA-B*51 as the primary susceptibility marker (P=6.82E-32, OR=3.82), with independent signals from HLA-B*57 and HLA-A*03. Outside the HLA region, the study confirmed IL23R (rs10889664: P=3.81E-12, OR=2.00), IL12A (rs1874886: P=1.62E-08, OR=1.61), and identified a novel association in the JRKL/CNTN5 region (rs2848479: P=3.29E-10, OR=1.66).

Traits studied:Behçet's disease

PubMed DOI Metascience Observatory

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Limited use of interleukin 28B in the setting of response-guided treatment with detailed on-treatment virological monitoring

ReviewAlessandra Mangia et al.(2011)· Hepatology

This is a special issue of the Italian medical journal BeAdfiles (September 2012) dedicated to genetic conditioning in HIV and hepatitis virus infections. It reviews the major genetic polymorphisms that influence disease progression, treatment response, and drug toxicity in HIV and chronic hepatitis B and C infections, with particular emphasis on IL28B polymorphisms (rs809917 and others) predicting HCV treatment response to interferon-alpha and ribavirin therapy, and ITPA gene variants protecting against ribavirin-induced anemia. The issue also covers pharmacogenetic markers (CYP2B6, ABCB1, HLA-B*5701) and their clinical applications in antiretroviral therapy.

Traits studied:AIDS progressionAntiretroviral therapy toxicityChronic hepatitis C sustained virological responseCreutzfeldt-Jakob diseaseDyslipidemiaEfavirenz side effectsHIV infection and progressionHepatitis B virus infectionHepatitis C genotype 1 response to interferonHepatitis C virus infectionHyperbilirubinemiaLeprosyLipodystrophyNeisseria meningitidis infectionNorovirus diarrheaPlasmodium falciparum malariaPlasmodium vivax malariaRenal impairmentRibavirin-induced anemiaTreatment response to interferon and ribavirinTuberculosis