Abstract
INTRODUCTION: Genetic studies have investigated the association of genetic variants with immunoglobulin G4-related disease (IgG4-RD). In this study, we summarize the results of genetic association in IgG4-RD. MATERIALS AND METHODS: We performed a literature search in MEDLINE, EMBASE via the OVID platform, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov (www. CLINICALTRIALS: gov ), and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) for genetic studies on IgG4-RD on January 20, 2023. RESULTS: We identified a total of 431 articles published between 1975 and 2023. After removing all the duplicates, we evaluated the abstract and selected 65 articles for full-text review. Among them, 17 fulfilled the eligibility criteria, including 15 original case-control studies, and two genome-wide association studies. Autoimmune pancreatitis was reported in 15 of the 17 articles, and the other 2 articles included IgG4-related periaortitis/periarteritis and general IgG4-RD subjects. A total of 52 polymorphisms in 25 genes were evaluated, including 13 polymorphisms in the 4 genes of the major histocompatibility complex (MHC) complex. The other genes are involved in different pathways. CONCLUSION: While MHC associations remain the strongest and most consistent across studies, our review identifies emerging non-MHC genetic loci such as KCNA3, CTLA4, PRSS1, and VPS13B, suggesting distinct immune- and tissue-specific pathways in different IgG4-RD phenotypes.