Supplementary Material for: Genetic association in Immunoglobulin G4 related disease: a Systematic Review

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 20/1/2023.
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 (GWAS). Autoimmune pancreatitis (AIP) was reported in 15 of the 17 articles, 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 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.