Department of Medicine II, Biometry and Epidemiology, University Hospital Munich-Grosshadern, Munich, Germany.
Digestion. 2011;84(1):29-35. doi: 10.1159/000321619. Epub 2011 Feb 8.
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.
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.
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).
The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC.
背景/目的：染色体 4q27 区域包含 IL2 和 IL21，是溃疡性结肠炎 (UC) 和各种其他自身免疫性疾病的既定风险位点。鉴于原发性硬化性胆管炎 (PSC) 与 UC 强烈吻合，以及原发性胆汁性肝硬化 (PBC) 患者中其他自身免疫性疾病的发病率增加，我们研究了 IL2/IL21 区域的遗传变异是否也可能调节这些两种罕见的胆汁淤积性肝病的易感性。
在 124 名 PBC 和 41 名 PSC 患者中，对 KIAA1109/TENR/IL2/IL21 连锁不平衡块内的 4 个与 UC 强烈相关的单核苷酸多态性 (SNP) 进行了基因分型。来自先前 UC 关联研究的 1487 名健康、无关的白种人对照等位基因频率可用。
所有 4 个标记的次要等位基因均与 PSC 易感性降低相关（rs13151961：p = 0.013，优势比 (OR) 0.34；rs13119723：p = 0.023，OR 0.40；rs6822844：p = 0.031，OR 0.41；rs6840978：p = 0.043，OR 0.46）。此外，由四个次要等位基因组成的单倍型对 PSC 易感性也具有保护作用（p = 0.0084，OR 0.28）。当排除伴有炎症性肠病的患者时，四个主要等位基因的单倍型与 PSC 独立相关（p = 0.033，OR 4.18）。
IL2/IL21 区域可能是 PSC 和 UC 的高度提示但迄今为止很少确定的共同易感性位点之一。
