A. Duthie et al., THE MAJOR HISTOCOMPATIBILITY COMPLEX INFLUENCES THE DEVELOPMENT OF CHRONIC LIVER-DISEASE IN MALE-CHILDREN AND YOUNG-ADULTS WITH CYSTIC-FIBROSIS, Journal of hepatology, 23(5), 1995, pp. 532-537
Background/Aims: Chronic liver disease is a well-recognised complicati
on 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 inapprop
riate 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 co
mplex has an important immunoregulatory role, we have investigated for
associations with this complex and chronic liver disease in cystic fi
brosis. 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 IU (complement component C4 and 21-hydr
oxylase) gene polymorphisms in 274 children and young adults with cyst
ic fibrosis, of whom 82 had evidence of chronic liver disease with por
tal hypertension in 49, and 146 healthy controls. Results: A marked di
fference in human leucocyte antigen frequency was limited to DQ6, whic
h was found in 66.7% of cystic fibrosis patients with liver disease co
mpared 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 p
atient group, namely DR15 and B7, When the patients were stratified fo
r the presence of portal hypertension, these observations were confirm
ed, 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 B
7-DR15-DQ6 may carry an increased risk of development of liver disease
in male cystic fibrosis patients. (C) Journal of Hepatology.