HLA and cytokine gene polymorphisms in biliary atresia.
OBJECTIVE
Extrahepatic biliary atresia remains one of the major hepatic causes of death in early childhood. Though a number of hypotheses have been developed to account for this disease, its aetiopathogenesis is poorly understood. One possibility is that this is an immune mediated disease which occurs following either toxic or infectious insult in a genetically susceptible host. Earlier studies suggested weak HLA associations but these remain unconfirmed. More recently studies of viral and autoimmune liver disease have begun to investigate non-MHC immunoregulatory gene polymorphisms.


METHODS
In the present study we used molecular genotyping to investigate selected HLA A, B, DRB1, DQA1, DQB1 and DPB1 alleles as well as polymorphisms in the interleukin-1 gene family, interleukin-10 promoter sequence and tumour necrosis factor alpha promoter genes in 101 children referred for surgical assessment with extra hepatic biliary atresia. Genotyping data were compared with those of 134 racially and geographically matched healthy adult health care workers.


CONCLUSIONS
Overall there were no statistically significant differences in the distribution of any of the genes tested comparing patients and controls. These data suggest that biliary atresia is not an HLA-associated disease and that polymorphisms in both the interleukin-1 and interleukin-10 genes are not risk factors for this disease.
Donaldson
Peter T
PT
Institute of Liver Studies, University Hospital Innsbruck Anichstrasse 356020 Innsbruck, Austria. p.t.donaldson@ncl.ac.uk
Clare
Michael
M
Constantini
Patrizia K
PK
Hadzic
Nedim
N
Mieli-Vergani
Giorginia
G
Howard
Edward
E
Kelley
Dympna
D
D000328:Adult; D001656:Biliary Atresia / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D007223:Infant; D007375:Interleukin-1 / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics*; D011110:Polymorphism, Genetic
D017931:DNA Primers; D006680:HLA Antigens; D007375:Interleukin-1; D016753:Interleukin-10