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Djilali-Saiah, I. et al.

Djilali-Saiah, Renous, Caillat-Zucman, Debray, Alvarez,

Linkage disequilibrium between HLA class II region and autoimmune hepatitis in pediatric patients.

BACKGROUND/AIMS: 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.[1]

References

Linkage disequilibrium between HLA class II region and autoimmune hepatitis in pediatric patients. Djilali-Saiah, I., Renous, R., Caillat-Zucman, S., Debray, D., Alvarez, F. J. Hepatol. (2004) [Pubmed]

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