Genetic association of beta-lactams-induced hypersensitivity reactions: A systematic review of genome-wide evidence and meta-analysis of candidate genes

ImportanceBeta-lactams (BLs) are the most prescribed antibiotics, being frequent cause of drug allergy. However, association between BL allergy and genetic variations is still unclear.ObjectiveThis systematic review meta-analysis aimed to summarize effects BL-induced hypersensitivity using existing evidence.MethodsWe searched PubMed, Medline, Scopus, EMBASE, CINAHL, Cochrane Library from inception September 15, 2022 with no language restriction. Genetic studies investigating variant/polymorphism risk drug-induced reactions among individuals receiving BL-antibiotics were included. We excluded acute interstitial nephritis, liver injury, serum sickness, isolated fever. Data comprehensively synthesized quality study assessed STrengthening Reporting Association Studies (STREGA). The record screening, extraction assessment performed by two reviewers discussions made resolve discrepancies. each variant pooled evaluated modified Venice criteria.ResultsA total 9276 records identified, 31 eligible for inclusion. Twenty-seven candidate-gene (5416 cases 5939 controls), while others next-generation sequencing (NGS) or genome-wide (GWASs) (119 838 1 487 111 controls). Forty-nine polymorphisms identified them located in allergic reaction pathways. Meta-analyses 15 candidate variants a mixture both immediate non-immediate revealed weak rs1801275 (8 studies; n = 1,560; odd ratio 0.73; 95%CI: 0.57–0.93) rs20541 (4 1,482; 1.34; 1.07–1.68) IL4R IL13, respectively. Results GWASs NGS confirmed associations HLA regions including HLA-DRA, HLA-B, HLA-DQA, HLA-DRB1, HLA-DRB3.ConclusionOur summarized evidence influencing estimated potential variants. postulated that genomic provide better insights mechanism suggest Class II results inconsistent unable generalize different settings. Further high-throughput well-defined function, epigenetic interaction, incorporated clinical factors, would be beneficial identification hypersensitivity.