J Hepatol 1995 Nov;23(5):532-7

The major histocompatibility complex influences the development of chronic live
disease in male children and young adults with cystic fibrosis

Duthie A, Doherty DG, Donaldson PT, Scott-Jupp R, Tanner MS, Eddleston AL, Mowat
AP
Department of Child Health, King's College Hospital Medical School, London, UK 
Abstract
BACKGROUND/AIMS: Chronic liver disease is a well-recognised complication of
cystic fibrosis. Recent reports suggest that its development is not determined
by specific mutations within the cystic fibrosis gene; however, familial
clustering of portal hypertension cases and inappropriate immune responses
against liver membrane antigens demonstrated in children with cystic fibrosis
and chronic liver disease suggest that other genetic loci may be relevant. As
the major histocompatibility complex has an important immunoregulatory role, we
have investigated for associations with this complex and chronic liver disease
in cystic fibrosis. METHODS: We have determined human leucocyte antigen class I
(A and B) and class II (DR) phenotypes by serological tissue typing and class II
(DR and DQ) and class III (complement component C4 and 21-hydroxylase) gene
polymorphisms in 274 children and young adults with cystic fibrosis, of whom 82
had evidence of chronic liver disease with portal hypertension in 49, and 146
healthy controls. RESULTS: A marked difference in human leucocyte antigen
frequency was limited to DQ6, which was found in 66.7% of cystic fibrosis
patients with liver disease compared to 32.9% of patients with no liver disease
(Pc < 0.03) and 28.8% of controls (Pc < 0.006). An increased frequency of the
two antigens in strong linkage disequilibrium with DQ6 was also observed within
this patient group, namely DR15 and B7. When the patients were stratified for
the presence of portal hypertension, these observations were confirmed, but the
human leucocyte antigen associations were significant only for male patients and
there was no association with the age of onset of liver disease. CONCLUSIONS:
These data suggest that the haplotype B7-DR15-DQ6 may carry an increased risk of
development of liver disease in male cystic fibrosis patients