BACKGROUND/AIMS: 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). CONCLUSION: The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC.
BACKGROUND/AIMS: 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). CONCLUSION: The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC.
Authors: Trine Folseraas; Espen Melum; Philipp Rausch; Brian D Juran; Eva Ellinghaus; Alexey Shiryaev; Jon K Laerdahl; David Ellinghaus; Christoph Schramm; Tobias J Weismüller; Daniel Nils Gotthardt; Johannes Roksund Hov; Ole Petter Clausen; Rinse K Weersma; Marcel Janse; Kirsten Muri Boberg; Einar Björnsson; Hanns-Ulrich Marschall; Isabelle Cleynen; Philip Rosenstiel; Kristian Holm; Andreas Teufel; Christian Rust; Christian Gieger; H-Erich Wichmann; Annika Bergquist; Euijung Ryu; Cyriel Y Ponsioen; Heiko Runz; Martina Sterneck; Severine Vermeire; Ulrich Beuers; Cisca Wijmenga; Erik Schrumpf; Michael P Manns; Konstantinos N Lazaridis; Stefan Schreiber; John F Baines; Andre Franke; Tom H Karlsen Journal: J Hepatol Date: 2012-04-18 Impact factor: 25.083
Authors: Maaike Biewenga; Sebastiaan Heidt; Manon Vergunst; Camiel M J Marijnissen; Rob A de Man; Annemiek A van der Eijk; Adriaan J van der Meer; Leendert A Trouw; Bart van Hoek Journal: JHEP Rep Date: 2022-02-22