Genetic Association of Beta-Lactams-Induced Hypersensitivity Reactions: A Protocol for Systematic Review and Meta-Analysis

Abstract

Beta-lactam (BL) antibiotics are among the drugs commonly related to hypersensitivity reactions. Several candidate gene studies and genome-wide association studies have reported associations of genetic variants and hypersensitivity reactions induced by BL antibiotics. However, the results were inconclusive. This protocol details a comprehensive systematic review of genetic factors associated with BL-induced hypersensitivity. A systematic search of literature related to genetic associations of BL-induced hypersensitivity will be performed through PubMed, Medline, Scopus, EMBASE, Web of Science, CINAHL, and the Cochrane central register of Controlled Trials (CENTRAL) from their inception dates with no language restrictions. Two reviewers will independently screen, extract, and appraise the risk of bias. Frequencies of genetic variants that comply with Hardy–Weinberg equilibrium will be extracted and pooled. Genetic models will be applied to variant effect calculation as per allele and genotype analysis. Based on statistical heterogeneity among studies, common effect estimation (odds ratio) and its corresponding 95% confidence interval will be analyzed. Sensitivity and subgroup analyses will be performed to determine the robustness of eligible studies. This systematic review and meta-analysis will provide comprehensive evidence of genetic effects regarding BL-induced hypersensitivity. The findings will enlighten the determination of disease-related genotypes that would potentially reveal allergy profiling in patients.

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

“…The pre-specified protocol has been published and registered at the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022300283). 24 The ethical consideration was exempted by the Ethical Committee of Faculty of Medicine, Chiang Mai University (EXEMPTION 8794/2022, FAC-MED-2565-08794) and no informed consent was applicable. The study was conducted following the Human Genome Epidemiology Network for the systematic review of genetic association studies guidance 25 and reported in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement ( Supplemental Table S1 ).…”

“…independently extracted relevant information using a predefined data extraction form described in a prespecified protocol. 24 Study characteristics, sample size, and diagnosis definition were collected, along with the genetic variants and their corresponding loci. Variants were extracted and labeled with the most current name and variant accession number according to National Center for Biotechnology Information (NCBI), and ClinVar databases.…”

Pharmacogenomics: Challenges and Future

“…In the final work, Lumkul et al [11] perform a systematic review and meta-analysis of genetic effects regarding beta-lactam (BL) antibiotics-induced hypersensitivity to aid the determination of disease-related genotypes, which could potentially facilitate allergy profiling in patients.…”