Primary biliary cirrhosis shows association with genetic polymorphism of tumour necrosis factor alpha promoter region

Background/Aims: Primary biliary cirrhosis is an autoimmune disease in whic h increased prevalence in first-degree relatives and an association with HL A DR8 suggest a genetic background, TNF alpha is a mediator of inflammation and immunity, and is implicated in the pathogenesis of primary biliary cir rhosis, ex vivo studies having shown reduced production of TNF alpha by lym phocytes from patients. Our group has previously described a biallelic prom oter-region polymorphism of the TNFA gene at position -308, and demonstrate d that the rare allele, TNF*2, has increased promoter function compared wit h the common allele, TNF*1. A further biallelic base change has been descri bed in the TNFA gene at -238, We conducted a case-control study to assess a ssociation of these gene polymorphisms with primary biliary cirrhosis. Methods: Ninety-one patients and 213 controls were genotyped for both TNFA loci using. restriction fragment length polymorphism analysis of PCR produc ts. Results: The high production TNFA-308*2 allele was significantly under- represented among subjects with primary biliary cirrhosis (27.5% PBC, 41.6% controls, p=0.02, pc=0.04, OR for carriage of TNF*1/*1 genotype=1.89, CI=1 .10-3.32). No association was shown with the TNFA -238 polymorphism. Conclusion: Primary biliary cirrhosis is associated with reduced carriage o f TNF*2, This is in keeping with a protective role of TNF alpha against the disease.