Polymorphisms in tumour necrosis factor alpha, interleukin-10 and transforming growth factor beta1 genes and end-stage liver disease.
OBJECTIVE
To determine any relationship between polymorphisms in the genes encoding tumour necrosis factor alpha (TNFalpha), interleukin-10 (IL-10) and transforming growth factor beta1 (TGFbeta1) 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 TGFbeta1 +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 auto-immune 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 TGFbeta1. No association between genotype and Child's class was found in primary biliary cirrhosis.


CONCLUSIONS
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 TNFalpha in vitro and may indicate a predisposition to these inflammatory conditions.
Bathgate
A J
AJ
Department of Medicine, Royal Infirmary of Edinburgh, UK. abathgate@ed.ac.uk
Pravica
V
V
Perrey
C
C
Hayes
P C
PC
Hutchinson
I V
IV
D000328:Adult; D000368:Aged; D005260:Female; D005819:Genetic Markers; D006801:Humans; D016753:Interleukin-10 / Q000032:analysis / Q000235:genetics*; D017093:Liver Failure / Q000235:genetics* / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011336:Probability; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics*
D005819:Genetic Markers; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10