Association between STAT4 polymorphisms and risk of primary biliary cholangitis: a meta-analysis

Area of Science:

• Immunogenetics
• Hepatology
• Genetics

Background:

• Primary biliary cholangitis (PBC) is a chronic, autoimmune liver disease.
• Previous studies suggest a link between signal transducer and activator of transcription 4 (STAT4) gene polymorphisms and PBC susceptibility.

Purpose of the Study:

• To conduct a comprehensive meta-analysis evaluating the association between STAT4 polymorphisms and the risk of PBC.
• To consolidate evidence from multiple studies to provide a more robust estimation of this genetic association.

Main Methods:

• A meta-analysis was performed including 13 eligible studies with 11,310 PBC cases and 27,844 controls.
• Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using fixed or random effects models.
• Sensitivity analyses and publication bias tests (Begg's test, Egger's regression) were conducted.

Main Results:

• Significant associations were found between several STAT4 polymorphisms (rs7574865, rs3024921, rs6752770, rs7601754, rs10168266) and increased PBC risk under the allelic model.
• The rs7574865 polymorphism showed significant association with PBC risk across all genotype models (dominant, recessive, co-dominant).
• Results remained stable in sensitivity analyses, and no significant publication bias was detected.

Conclusions:

• STAT4 gene polymorphisms, specifically rs7574865, rs3024921, rs6752770, rs7601754, and rs10168266, are significantly associated with an increased risk of primary biliary cholangitis.
• These findings reinforce the role of STAT4 in the genetic susceptibility to PBC.
• Further research may explore the functional implications of these STAT4 variants in PBC pathogenesis.