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Lookup NU author(s): Dr Kaushik Agarwal, Professor David Jones, Dr Peter Donaldson
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Genetic susceptibility to type 1 autoimmune hepatitis is indicated by a preponderance of female subjects and strong associations with human leukocyte antigens (HLA) DRB1*0301 and DRB1*0401. The gene encoding cytotoxic T- lymphocyte antigen-4 (CTLA-4) on chromosome 2q33 may also influence autoimmunity. To determine the frequency and significance of the exon 1 adenine (A)-guanine (G) base-exchange polymorphism for CTLA-4 in patients with type 1 autoimmune hepatitis, 155 northern European Caucasoid patients and 102 ethnically-matched control subjects were tested by polymerase chain reaction. The genotype distribution was significantly different in patients compared to controls (AA = 50/155 patients vs. 51/102 controls; AG = 84/155 patients vs. 38/102 controls; GG = 21/155 patients vs. 13/102 controls, χ2 = 8.94, P = .011). This difference was caused by a significant over- representation of the G allele in patients compared to controls (105/155 patients vs. 51/102 controls, χ2 = 8.34, P = .004, odds ratio = 2.12). The GG genotype was associated with a significantly higher mean serum aspartate transaminase level (P = .03), greater frequency of antibodies to thyroid microsomal antigens (P = .004) and was found more commonly in patients with HLA DRB1*0301 (P = .02). Treatment outcomes, however, were not affected by the genotype. The CTLA-4 G allele is more common in patients with type 1 autoimmune hepatitis and may represent a second susceptibility allele. Furthermore, there may be synergy between the HLA-DRB1 *0301 and the GG genotype in terms of disease risk.
Author(s): Agarwal K, Czaja AJ, Jones DEJ, Donaldson PT
Publication type: Article
Publication status: Published
Journal: Hepatology
Year: 2000
Volume: 31
Issue: 1
Pages: 49-53
ISSN (print): 0270-9139
ISSN (electronic): 1527-3350
Publisher: John Wiley & Sons
URL: http://dx.doi.org/10.1002/hep.510310110
DOI: 10.1002/hep.510310110
PubMed id: 10613727
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