A web resource for mining HLA associations with adverse drug reactions: HLA-ADR

Abstract

Human leukocyte antigens (HLA) are an important family of genes involved in the immune system. Their primary function is to allow the host immune system to be able to distinguish between self and non-self peptides—e.g. derived from invading pathogens. However, these genes have also been implicated in immune-mediated adverse drug reactions (ADRs), presenting a problem to patients, clinicians and pharmaceutical companies. We have previously developed the Allele Frequency Net Database (AFND) that captures the allelic and haplotype frequencies for these HLA genes across many healthy populations from around the world. Here, we report the development and release of the HLA-ADR database that captures data from publications where HLA alleles and haplotypes have been associated with ADRs (e.g. Stevens–Johnson Syndrome/toxic epidermal necrolysis and drug-induced liver injury). HLA-ADR was created by using data obtained through systematic review of the literature and semi-automated literature mining. The database also draws on data already present in AFND allowing users to compare and analyze allele frequencies in both ADR patients and healthy populations. The HLA-ADR database provides clinicians and researchers with a centralized resource from which to investigate immune-mediated ADRs.Database URL: http://www.allelefrequencies.net/hla-adr/.

Associations of HLA genotypes with antithyroid drug‐induced agranulocytosis: A systematic review and meta‐analysis of pharmacogenomics studies

“…Second, oxidative drug metabolites induce T‐cell mediated reactions against proliferation and differentiation of pluripotent haematopoietic stem cells in the bone marrow . High levels of polymorphism and heterogeneity of HLA gene not only play a crucial role in immune regulation but also increase the chance of various ADRs, for example, HLA‐B*15:02 and carbamazepine‐induced Stevens–Johnson syndrome/toxic epidermal necrolysis, HLA‐A*31:01 and carbamazepine‐induced drug reaction with eosinophilia and systemic symptoms, HLA‐B*13:01 and dapsone‐induced drug reaction with eosinophilia and systemic symptoms, HLA‐B*58:01 and allopurinol‐induced severe cutaneous adverse reaction, and HLA‐B*57:01 and abacavir hypersensitivity . For drug‐induced agranulocytosis, genetic susceptibility with single amino acid changes in HLA‐DQB1 (126Q) and HLA‐B (158 T) was associated with clozapine‐induced agranulocytosis .…”

Causative Drugs of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Israel

“…The Israeli population, currently counting 8 522 200 citizens, is unique in its composition, mostly Jews (75%) and Muslim Arabs (21%), 20 both genetically distinguished from most white populations. [21][22][23][24][25] Yet, the majority of information presented in Israeli drug labels and patient leaflets relies on data obtained abroad, mostly in Europe and the United States. The results presented here highlight the need for epidemiological studies in the Israeli population.…”

High and variable population prevalence of HLA‐B*56:02 in indigenous Australians and relation to phenytoin‐associated drug reaction with eosinophilia and systemic symptoms

“…A publicly available allele frequency database (http://www.allelefrequencies.net/) was searched to find data on HLA‐B*56:02, B*15:02 and B*15:13 frequencies in different Indigenous Australian communities and Europeans living in Australia …”