A study on UGT1A1 and ABCG8 gene polymorphism: meta-analysis and bioinformatics approach in the etiology of gallstone disease

Abstract Background Gallstone disease (GSD) is a prevalent chronic hepatobiliary condition characterized by impaired metabolism of cholesterol, bilirubin, and bile acids. Gallstones are categorized as cholesterol, pigment (black and brown), or mixed stones. Genetic predisposition accounts for approximately 25% of cases, with multiple variants influencing GSD susceptibility. Objective This study investigates the association of UGT1A1 ( rs6742078 ) and ABCG8 ( rs11887534 ) polymorphisms with GSD through a meta-analysis, bioinformatics assessment of non-synonymous SNPs (nsSNPs). Methods A systematic review of studies ( UGT1A1 and ABCG8 from January 2000 to January 2020) was conducted using databases such as PubMed, Embase, Scopus, and Web of Science. Meta-analyses pooled data from 6492 cases and 59,635 controls for UGT1A1 , and 2628 cases and 1744 controls for ABCG8 . Comprehensive Meta-Analysis 3.0 software was used, applying fixed/random-effects models based on heterogeneity ( I 2 > 50%, p < 0.1). Bioinformatics tools evaluated nsSNP deleteriousness and protein stability. Results The UGT1A1 rs6742078 variant was significantly associated with GSD (OR 1.119, 95% CI 1.017–1.232, p = 0.022). For ABCG8 rs11887534 , the association was stronger (OR 2.573, 95% CI 1.988–3.329, p < 0.001). Bioinformatic analyses predicted both UGT1A1 rs72551341 and ABCG8 rs11887534 nsSNPs as deleterious, leading to reduced protein stability and likely phenotypic consequences. Conclusion The meta-analysis confirms significant associations of UGT1A1 rs6742078 and ABCG8 rs11887534 polymorphisms with GSD, implicating glucuronidation and cholesterol transport pathways in disease etiology. Future studies should focus on functional analysis of these polymorphisms to enhance understanding of genetic predisposition to GSD and inform preventive strategies.