Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

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. Copyright (C) 2011 S. Karger AG, Basel