title: Cytotoxic T lymphocyte antigen-4 +49A/G polymorphism does not affect susceptibility to autoimmune hepatitis.
abstract: OBJECTIVE
  Single nucleotide polymorphisms (SNP) in the Cytotoxic T lymphocyte antigen-4 gene (CTLA-4) have been associated with several autoimmune diseases including autoimmune Hepatitis (AIH). In this chronic idiopathic inflammatory liver disease, conflicting results have been reported on the association with a SNP at position +49 in the CTLA-4 gene in small patient cohorts. Here, we established the role of this SNP in a sufficiently large cohort of AIH patients.
  
  
  METHODS
  The study population consisted of 672 AIH patients derived from academic and regional hospitals in the Netherlands and was compared with 500 controls selected from the 'Genome of the Netherlands' project cohort. Genotype frequencies were assessed by PCR for patients and by whole genome sequencing for controls.
  
  
  RESULTS
  No significant differences in allele frequencies were found between patients and controls (G Allele: 40% vs 39%, P = 0.7). Similarly, no significant differences in genotype frequencies between patients and controls were found. Finally, there was no relation between disease activity and the G allele or AG and GG genotypes.
  
  
  CONCLUSIONS
  The Cytotoxic T Lymphocyte Antigen-4 +49 A/G polymorphism does not represent a major susceptibility risk allele for AIH in Caucasians and is not associated with disease severity at presentation.
authors.affiliation: Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Nicole M F
authors.initials: NM
authors.lastname: van Gerven
authors.forename: Ynto S
authors.initials: YS
authors.lastname: de Boer
authors.forename: Antonie
authors.initials: A
authors.lastname: Zwiers
authors.forename: Bart
authors.initials: B
authors.lastname: van Hoek
authors.forename: Karel J
authors.initials: KJ
authors.lastname: van Erpecum
authors.forename: Ulrich
authors.initials: U
authors.lastname: Beuers
authors.forename: Henk R
authors.initials: HR
authors.lastname: van Buuren
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
authors.forename: Jannie W
authors.initials: JW
authors.lastname: den Ouden
authors.forename: Robert C
authors.initials: RC
authors.lastname: Verdonk
authors.forename: Ger H
authors.initials: GH
authors.lastname: Koek
authors.forename: Johannes T
authors.initials: JT
authors.lastname: Brouwer
authors.forename: Maureen M J
authors.initials: MM
authors.lastname: Guichelaar
authors.forename: Jan M
authors.initials: JM
authors.lastname: Vrolijk
authors.forename: G
authors.initials: G
authors.lastname: Kraal
authors.forename: Chris J J
authors.initials: CJ
authors.lastname: Mulder
authors.forename: Carin M J
authors.initials: CM
authors.lastname: van Nieuwkerk
authors.forename: Gerd
authors.initials: G
authors.lastname: Bouma
mesh_terms: D000704:Analysis of Variance; D060908:CTLA-4 Antigen / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D019693:Hepatitis, Autoimmune / Q000235:genetics*; D006801:Humans; D009426:Netherlands; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics*
chemical_list: D060908:CTLA-4 Antigen
keywords: autoimmune hepatitis; cytotoxic T lymphocyte antigen-4; genotype; single nucleotide polymorphism; susceptibility