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Link found between genes and penicillin allergy

Monday September 7th 2020

A link between genes and penicillin allergy has been discovered by an international team of scientists.

The researchers, who used data from 600,000 individuals’ records collected in biobanks in Estonia, UK and USA, identified genetic risk factors underlying penicillin-induced hypersensitivity reactions.

The genome-wide association study (GWAS) of self-reported penicillin allergy in the different biobanks revealed a locus located in the major histocompatibility complex (MHC) I gene HLA-B.

This was further narrowed down to the HLA-B*55:01 allele and researchers found that allele carriers had a 33% higher relative odds of penicillin allergy.

The study, which is published in The American Journal of Human Genetics, also detected a genome-wide significant missense variant in the PTPN22 gene, which has been associated with several autoimmune diseases and drug-induced liver injury.

Study first author Dr Kristi Krebs said: “When examining other conditions associated with the HLA-B*55:01 allele, we found a significant association with lower white blood cell counts.

“Further, the top hit overlapped with regions found to have regulatory function in T-cells and correlated with the expression levels of PSORS1C3, which has previously been associated with hypersensitivity reactions to several medications.

“These findings together raise the possibility that the variant may predispose to a T-cell-mediated process leading to a delayed penicillin reaction.”

Lead author Dr João Fadista said that an analysis of the genome-wide genetic correlation of the self-reported penicillin allergy results also revealed an overlap with the rheumatoid arthritis and psoriasis.

“This, together with the finding in the PTPN22 gene, indicates a possible underlying autoimmune factor in the development of penicillin allergy investigated in our study,” he added.

The research was carried out by Estonian Genome Centre, University of Tartu, Statens Serum Institut, University of Oxford, Vanderbilt University Medical Center, Harvard Medical School, Broad Institute of MIT and Harvard, and 23andMe.

Krebs K, Bovijn J, Zheng N et al. Genome-wide Study Identifies Association between HLA-B?55:01 and Self-Reported Penicillin Allergy. The American Journal of Human Genetics 3 September 2020

https://www.cell.com/ajhg/fulltext/S0002-9297(20)30276-7

Tags: Allergies & Asthma | Europe | Genetics | North America | Pharmaceuticals | UK News

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