Linkage disequilibrium between HLA class II region and autoimmune hepatitis in pediatric patients.
OBJECTIVE
Susceptibility HLA class II alleles associated with autoimmune hepatitis (AIH) were only described in case-control studies.


METHODS
The transmission/disequilibrium test was used in 50 simplex families with AIH, to determine if affected offspring received the disease-associated allele more frequently than its alternate. HLA-DRB1 and DQB1 allele genotyping and autoimmune regulator (AIRE) polymorphisms located in exons 6, 8 and 10 were investigated by PCR-based methods.


RESULTS
HLA-DRB1*03 allele was significantly transmitted from heterozygous parent to affected offspring (81.5%) with type 1 AIH compared to random expected frequency (50.0%; P=0.004) or to unaffected offspring (42.8%; P=0.03). HLA-DRB1*1301 allele showed an excess transmission to affected children (100%) than expected frequency (P<0.0001) or unaffected offspring (P=0.001). The transmission of DQB1*201 or DQB1*0603 alleles showed significant deviation in patients compared to random frequencies: (84.8%; P<0.0001 for DQB1*0201 or 100%; P<0.0001 for DQB1*0603). HLA-DQB1*0201 showed a strong association with type 2 AIH in children (100.0%, P=0.0005).


CONCLUSIONS
HLA-DRB1 gene is the major genetic determinant in HLA class II region for children with type 1 AIH. Type 2 AIH is associated with the HLA-DQB1gene. Finally, AIRE gene abnormality does not contribute to the development of isolated AIH.
Djilali-Saiah
Idriss
I
Gastroenterology Division, Hôpital Sainte-Justine, 3175, Côte Sainte-Catherine, Montreal, Que., Canada. isaiah@justine.umontreal.ca
Renous
Reginald
R
Caillat-Zucman
Sophie
S
Debray
Dominique
D
Alvarez
Fernando
F
D000293:Adolescent; D002170:Canada; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D005602:France; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D019693:Hepatitis, Autoimmune / Q000235:genetics* / Q000276:immunology*; D006579:Heterozygote; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D015810:Linkage Disequilibrium; D011110:Polymorphism, Genetic
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II