| Literature DB >> 25611558 |
N M F van Gerven1, Y S de Boer1, A Zwiers2, B J Verwer1, J P H Drenth3, B van Hoek4, K J van Erpecum5, U Beuers6, H R van Buuren7, J W den Ouden8, R C Verdonk9, G H Koek10, J T Brouwer11, M M J Guichelaar12, J M Vrolijk13, M J Coenraad4, G Kraal14, C J J Mulder1, C M J van Nieuwkerk1, E Bloemena15, H W Verspaget3, V Kumar16, A Zhernakova16, C Wijmenga16, L Franke16, G Bouma2.
Abstract
The classical human leukocyte antigen (HLA)-DRB1*03:01 and HLA-DRB1*04:01 alleles are established autoimmune hepatitis (AIH) risk alleles. To study the immune-modifying effect of these alleles, we imputed the genotypes from genome-wide association data in 649 Dutch AIH type-1 patients. We therefore compared the international AIH group (IAIHG) diagnostic scores as well as the underlying clinical characteristics between patients positive and negative for these HLA alleles. Seventy-five percent of the AIH patients were HLA-DRB1*03:01/HLA-DRB1*04:01 positive. HLA-DRB1*03:01/HLA-DRB1*04:01-positive patients had a higher median IAIHG score than HLA-DRB1*03:01/HLA-DRB1*04:01-negative patients (P<0.001). We did not observe associations between HLA alleles and alanine transaminase levels (HLA-DRB1*03:01: P=0.2; HLA-DRB1*04:01; P=0.5); however, HLA-DRB1*03:01 was independently associated with higher immunoglobulin G levels (P=0.04). The HLA-DRB1*04:01 allele was independently associated with presentation at older age (P=0.03) and a female predominance (P=0.04). HLA-DRB1*03:01-positive patients received immunosuppressive medication and liver transplantation. In conclusion, the HLA-DRB1*03:01 and HLA-DRB1*04:01 alleles are both independently associated with the aggregate diagnostic IAIHG score in type-1 AIH patients, but are not essential for AIH development. HLA-DRB1*03:01 is the strongest genetic modifier of disease severity in AIH.Entities:
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Year: 2015 PMID： 25611558 DOI： 10.1038/gene.2014.82
Source DB: PubMed Journal: Genes Immun ISSN： 1466-4879 Impact factor: 2.676