title: Analysis of IL2/IL21 gene variants in cholestatic liver diseases reveals an association with primary sclerosing cholangitis.
abstract: OBJECTIVE
  The chromosome 4q27 region harboring IL2 and IL21 is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the IL2/IL21 region may also modulate the susceptibility to these two rare cholestatic liver diseases.
  
  
  METHODS
  Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients. Control allele frequencies from 1,487 healthy, unrelated Caucasians were available from a previous UC association study.
  
  
  RESULTS
  The minor alleles of all four markers were associated with a decreased susceptibility to PSC (rs13151961: p = 0.013, odds ratio (OR) 0.34; rs13119723: p = 0.023, OR 0.40; rs6822844: p = 0.031, OR 0.41; rs6840978: p = 0.043, OR 0.46). Moreover, a haplotype consisting of the four minor alleles also had a protective effect on PSC susceptibility (p = 0.0084, OR 0.28). A haplotype of the four major alleles was independently associated with PSC when excluding the patients with concomitant inflammatory bowel disease (p = 0.033, OR 4.18).
  
  
  CONCLUSIONS
  The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC.
authors.affiliation: Department of Medicine II, Biometry and Epidemiology, University Hospital Munich-Grosshadern, Munich, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Stallhofer
authors.forename: Gerald Ulrich
authors.initials: GU
authors.lastname: Denk
authors.forename: Jürgen
authors.initials: J
authors.lastname: Glas
authors.forename: Rüdiger Paul
authors.initials: RP
authors.lastname: Laubender
authors.forename: Burkhard
authors.initials: B
authors.lastname: Göke
authors.forename: Christian
authors.initials: C
authors.lastname: Rust
authors.forename: Stephan
authors.initials: S
authors.lastname: Brand
authors.forename: Thomas
authors.initials: T
authors.lastname: Pusl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D015209:Cholangitis, Sclerosing / Q000235:genetics* / Q000276:immunology; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D007378:Interleukins / Q000235:genetics*; D008105:Liver Cirrhosis, Biliary / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: C508594:IL2 protein, human; D007376:Interleukin-2; D007378:Interleukins; D000098546:Interleukin-21