Polymorphisms in tumour necrosis factor α, interleukin-10 and transforming growth factor β1 genes and end-stage liver disease

Abstract

Objective: To determine any relationship between polymorphisms in the genes encoding tumour necrosis factor α (TNFα), interleukin-10 (IL-10) and transforming growth factor β1 (TGFβ1) and end-stage liver disease. Methods: Whole-blood samples were taken from patients attending the Scottish Liver Transplant Unit with end-stage liver disease (primary biliary cirrhosis, n = 61; alcoholic liver disease, n = 25; primary sclerosing cholangitis, n = 17; viral disease, n = 8; type 1 auto-immune hepatitis, n = 8; acute liver failure, n = 20). DNA was extracted and the polymorphisms at positions TNF -308, IL-10 -1082 and TGFβ1 +869 and +915 were determined using sequence-specific oligonucleotide probes. Samples were also analysed from normal healthy controls. Results: There was a significant difference between patients with primary sclerosing cholangitis and healthy controls, with 65% of patients (11/17) possessing at least one TNF2 allele (A at position -308) compared with 38% of controls (P =0.02). Four of the eight patients with autoimmune hepatitis were homozygous for TNF2 while the other four were heterozygous (P = 0.001). No significant difference between controls and patients was seen in polymorphisms for IL-10 or TGFβ1. No association between genotype and Child's class was found in primary biliary cirrhosis. Conclusion: Patients with primary sclerosing cholangitis and auto-immune hepatitis are more likely to possess TNF2 than normal controls. This allele has been associated with an increased production of TNFα in vitro and may indicate a predisposition to these inflammatory conditions. © 2000 Lippincott Williams & Wilkins.