Supplementary Material for: Analysis of <i>IL2/IL21</i> Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis
2011-02-08T00:00:00Z (GMT) by
<i>Background/Aims:</i> The chromosome 4q27 region harboring <i>IL2</i> and <i>IL21</i> 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 <i>IL2/IL21</i> region may also modulate the susceptibility to these two rare cholestatic liver diseases. <i>Methods:</i> Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the <i>KIAA1109/TENR/IL2/IL21</i> 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. <i>Results:</i> 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). <i>Conclusion:</i> The <i>IL2/IL21</i> region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC.