Impact of SNP rs2187668 in HLA-DQA1 on clinical presentation and treatment response in patients with type-1 autoimmune hepatitis

AF Stättermayer; M Eder; S Beinhardt; K Kozbial; C Freissmuth; F Wrba; M Trauner; P Ferenci; H Hofer

doi:10.1055/s-0035-1551768

Zeitschrift für Gastroenterologie, Table of Contents

Impact of SNP rs2187668 in HLA-DQA1 on clinical presentation and treatment response in patients with type-1 autoimmune hepatitis

AF Stättermayer ¹, M Eder ¹, S Beinhardt ¹, K Kozbial ¹, C Freissmuth ¹, F Wrba ², M Trauner ¹, P Ferenci ¹, H Hofer ¹

¹Medizinische Universität Wien, Abteilung für Gastroenterologie und Hepatologie, Wien, Austria
²Medizinische Universität Wien, Institut für Klinische Pathologie, Wien, Austria

Abstract

Background/aim: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease with limited etiopathogenetic understanding. Recently, a genome-wide association study (GWAS) identified a single nucleotide polymorphism (SNP, rs2187668) in the HLA-DQA1 gene, which is strongly associated with AIH type-1. We therefore evaluated the impact of this SNP on clinical presentation and treatment response in patients with AIH.

Methods: One-hundred and six patients with type-1 AIH (female: 82 [77.4%], mean age: 43.1 [CI95%: 39.7 – 46.5] years), who reached a probable or definite score according to the simplified or revised scoring system were evaluated. SNP rs2187668 was investigated by real-time-PCR in all patients with AIH and in a control group of 97 healthy subjects.

Results: Sixty-one (57.5%) patients with AIH had rs2187668 genotype CC, 38 (35.8%) were heterozygous and 7 (6.6%) had genotype TT. Minor allele frequency (MAF) of the risk allele (T) was 24.5% and was significantly higher than in the control group (MAF: 7.2%; p < 0.001). T allele carriers with AIH had significantly higher levels of immune globulin G (IgG) than patients with CC: 1.55 (CI95%: 1.36 – 1.74) x ULN vs. 1.32 (CI95%: 1.18 – 1.46) x ULN, respectively (p = 0.040). Nevertheless, no differences in ALT or AST levels were observed between the two groups. Further, age at diagnosis as well as presence of cirrhosis were equally distributed across different genotypes. Response to immunosuppressive treatment at 12 months did not differ between rs2187668 T allele carriers and patients with CC genotype.

Conclusion: The T allele in rs2187668 in HLA-DQA1 is strongly associated with AIH in our cohort of patients. Rs2187668 might influence disease activity, although no effect on response to immunosuppressive treatment could be observed.