Polymorphisms in tumour necrosis factor alpha, interleukin-10 and transforming growth factor beta 1 genes and end-stage liver disease

Objective To determine any relationship between polymorphisms in the genes encoding tumour necrosis factor alpha (TNF alpha), interleukin-10 (IL-10) a nd transforming growth factor beta1 (TGF beta1) 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 cirrho sis, n = 61; alcoholic liver disease, n = 25; primary sclerosing cholangiti s, 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 positio ns TNF - 308, IL-10 - 1082 and TGF beta1 +869 and +915 were determined usin g sequence-specific oligonucleotide probes. Samples were also analysed from normal healthy controls. Results There was a significant difference between patients with primary sc lerosing cholangitis and healthy controls, with 65% of patients (11/17) pos sessing 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 w ere homozygous for TNF2 while the other four were heterozygous (P = 0.001). No significant difference between controls and patients was seen in polymo rphisms for IL-10 or TGF beta1. No association between genotype and Child's class was found in primary biliary cirrhosis. Conclusion Patients with primary sclerosing cholangitis and auto-immune hep atitis are more likely to possess TNF2 than normal controls. This allele ha s been associated with an increased production of TNF alpha in vitro and ma y indicate a predisposition to these inflammatory conditions. Eur J Gastroe nterol Hepetol 12:1329-1333 (C) 2000 Lippincott Williams & Wilkins.