Abstract
BACKGROUND: Chronic urticaria (CU) is a heterogeneous skin disorder whose genetic drivers are incompletely defined. OBJECTIVE: To systematically review and meta-analyse genetic and epigenetic factors that influence susceptibility and treatment response in acute and CU. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed, Scopus and Web of Science were searched from inception to 31 July 2024. Original human studies reporting genetic or epigenetic associations with any urticaria subtype were eligible. Random-effects meta-analyses were undertaken when at least three comparable datasets were available. RESULTS: Sixty-one studies met the inclusion criteria. Associations were confirmed for HLA-B44 (pooled Odds Ratio 8.15, 95% Confidence Interval 1.61-41.29; I(2) = 86%) and vitamin-D-receptor polymorphisms FokI, TaqI and BsmI, each conferring a 1.5- to 2.1-fold increased risk. Variants in CRTH2, FcεR1α and C-reactive protein predicted antihistamine response, while FCER1G, IL-6, prostaglandin-endoperoxide synthase 2, CCL2 and TNF-pathway genes were over-expressed in lesional tissue, supporting an immune-mediated pathogenesis. Evidence for non-CSU subtypes, acute urticaria, epigenetic modifications and gene-environment interactions was limited. CONCLUSIONS: CU displays an autoimmune-like genetic signature. HLA-B44 and vitamin D receptor variants are susceptibility markers, and pharmacogenetic signals enable personalised therapy. Longitudinal studies integrating environmental exposures and functional genomics are needed to translate these insights into precision care.