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Purpose  The precise etiology of autoimmune hepatitis (AIH) remains unknown, although a number of genetic loci have been implicated in the susceptibility of type 1 AIH. The purpose of this study was to test for association of these loci with type 1 AIH in New Zealand Caucasians.    Methods  77 AIH patients and 485 healthy controls were genotyped for the SNPs rs2187668 ( HLA-DRB*03:01 ), rs660895 ( HLA-DRB*04:01 ), rs3749971 ( HLA-A1-B8-DR3 ), rs231775 ( CLTLA4 ), rs1800629 ( TNF ), and rs1800682 ( FAS ) using predesigned TaqMan SNP genotyping assays. Chi square analysis was used to test for association of allele and genotype with overall AIH, and with severe fibrosis and ALT levels at 6 months.    Results  Significant risk of AIH was conferred by the minor alleles of rs2187668 (OR = 2.45, 95% CI 1.65-3.61, p < 0.0001), rs3749971 (OR = 1.89, 95% CI 1.21-2.94, p = 0.004) and rs1800629 (OR = 2.06, 95% CI 1.41-3.01, p = 0.0001). Multivariate analysis showed that rs2187668 was independently associated with type 1 AIH susceptibility (OR = 2.40, 95% CI 1.46-3.93, p = 0.001). The C allele of  FAS  SNP rs1800682 was associated with increased risk of severe fibrosis at diagnosis (OR = 2.03, 95% CI 1.05-3.93, p = 0.035) and with incomplete normalization of ALT levels at 6 months post-diagnosis (OR = 3.94, 95% CI 1.62-9.54, p = 0.0015).    Conclusions  This is the first population-based study to investigate genetic risk loci for type 1 AIH in New Zealand Caucasians. We report significant independent association of  HLA-DRB1*03:01  with overall susceptibility to type 1 AIH, as well as  FAS  with a more aggressive disease phenotype.

Association of the HLA locus and TNF with type I autoimmune hepatitis susceptibility in New Zealand Caucasians