Multiple studies indicate a possible correlation between ADD3 rs2501577 and biliary atresia susceptibility; however, a conclusive determination has yet to be made. Objective:Investigate the role of ADD3 rs2501577 in biliary atresia susceptibility across diverse populations.

Importance: Multiple studies indicate a possible correlation between ADD3 rs2501577 and biliary atresia susceptibility; however, a conclusive determination has yet to be made. Objective: Investigate the role of ADD3 rs2501577 in biliary atresia susceptibility across diverse populations. Data Sources: The study protocol has been registered on PROSPERO, an international platform for systematic review registration (PROSPERO ID: CRD42023384641). The following databases will be searched until February 1, 2023: PubMed, Embase, Cochrane, CBM, Web of Science, and CNKI. Study Selection: Eight studies were selected from seven papers to assess the data. A total of 7,651 participants were included, consisting of 1,662 in the BA group and 5,989 in the NC group. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed while conducting the systematic reviews and meta-analyses. Two authors independently assessed the quality of the included studies using the Newcastle–Ottawa Quality Assessment Scale. The significance of the pooled odds ratio (OR) was evaluated with a Z test, and statistical heterogeneity across studies was assessed using the I2 and Q statistics. Publication bias was assessed using Egger’s and Begg’s tests. Main Outcome(s) and Measure(s): The primary study outcome was the development of biliary atresia. Subgroup analysis was performed based on race, region, and assessment of Hardy-Weinberg equilibrium (HWE). Results: The studies indicate that the ADD3 rs2501577 susceptibility locus increases the risk of developing biliary atresia, regardless of allelic, homozygote, dominant, and recessive gene inheritance models. Furthermore, ADD3 has been found to be associated with apoptosis, cell cycle, and cell damage repair based on functional analysis. Conclusions and Relevance: The ADD3 rs2501577 polymorphic locus is associated with an increased risk of biliary atresia, particularly in Asian populations. This study recommends further investigation of the ADD3 rs2501577 locus in Asian populations to validate its role in the diagnosis of biliary atresia.