Researchers have reported the first robust piece of evidence for the role of the major histocompatibility complex (MHC) gene HLA-B in penicillin allergy.
Estimates indicate that in the USA adverse drug reactions (ADRs) account for 6.7% of hospitalisations and cause more than 100,000 deaths annually. ADRs are typically divided into two types of reactions. Type A reactions relate to the pharmacological action of a drug and are much more predictable. Whereas, type B reactions are idiosyncratic, less predictable, largely dose independent and typically driven by hypersensitivity reactions. While type B reactions are less frequent, they tend to be more severe. One of the most common causes of type B reactions are antibiotics.
The prevalence of penicillin allergy is estimated to be as high as 25% in some settings. Nonetheless, there have been relatively few studies exploring the genetic determinants of penicillin allergy. As a result, the need to better understand the mechanisms and risk factors that contribute to these reactions is vital.
In a study, published in AJHG, researchers sought to identify genetic risk factors underlying penicillin-induced hypersensitivity reactions. The team utilised data from the electronic health records of more than 600,000 participants from the UK, Estonian and Vanderbilt University Medical Center’s BioVU biobanks. They further replicated their results in the 23andMe research cohort, involving a total of 1.12 million individuals.
Genome-wide meta-analysis revealed two loci associated with penicillin allergy. This included one located in the HLA region on chromosome 6. Fine-mapping of this signal pinpointed to the HLA-B∗55:01 allele which was confirmed in 23andMe’s research cohort. The lead SNP was associated with lower lymphocyte counts. Overall, carriers of this allele were found to have a 33% higher relative odds of penicillin allergy. The other hit was in PTPN22, which is correlated with the genetics of rheumatoid arthritis and psoriasis.
The team’s results were presented at the recent American Society of Human Genetics 2020 Virtual Meeting by Kristi Krebs, PhD student, University of Tartu (Estonia). Krebs noted that more research is needed to determine the precise immune processes involved in penicillin allergy. In turn, this would provide more clinically actionable insight into genetic risk factors underlying hypersensitivity to the antibiotic. These findings highlight the power of using biobanks linked with electronic health records to identify significant results.
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