Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
PLoS One. 2012;7(9):e44380. doi: 10.1371/journal.pone.0044380. Epub 2012 Sep 11.
Previous studies implicated that IL23R and IL17 genes play an important role in autoimmune inflammation. Genome-wide association studies have also identified multiple single nucleotide polymorphisms (SNPs) in the IL23R gene region associated with inflammatory bowel diseases. This study examined the association of IL23R and IL17A gene SNPs with ulcerative colitis susceptibility in a population in China.
A total of 270 ulcerative colitis and 268 healthy controls were recruited for the analyses of 23 SNPs in the IL23R and IL17A regions. Genomic DNA was extracted and analysis of these 23 SNPs using ligase detection reaction allelic (LDR) technology. Genotype and allele associations were calculated using SPSS 13.0 software package.
Compared to the healthy controls, the variant alleles IL23R rs7530511, and rs11805303 showed a statistically significant difference for ulcerative colitis susceptibility (0.7% vs 3.3%, P = 0.002; 60.4% vs 53.2%, P = 0.0017, respectively). The linkage disequilibrium (LD) patterns of these SNPs were measured and three LD blocks from the SNPs of IL23R and one block from those of IL17A were identified. A novel association with ulcerative colitis susceptibility occurred in haplotypes of IL23R (Block1 H3 P = 0.02; Block2 H2 P = 0.019; Block3 H4 P = 0.029) and IL17A (H4 P = 0.034). Pair-wise analyses showed an interaction between the risk haplotypes in IL23R and IL17A (P = 0.014).
Our study demonstrated that rs7530511, and rs11805303 of IL23R were significantly associated with ulcerative colitis susceptibility in the Chinese population. The most noticeable finding was the linkage of IL23R and IL17A gene region to ulcerative colitis risk due to the gene-gene interaction.
先前的研究表明，IL23R 和 IL17 基因在自身免疫性炎症中发挥重要作用。全基因组关联研究还在 IL23R 基因区域鉴定出多个与炎症性肠病相关的单核苷酸多态性（SNP）。本研究在中国人群中研究了 IL23R 和 IL17A 基因 SNP 与溃疡性结肠炎易感性的关联。
共招募 270 例溃疡性结肠炎患者和 268 例健康对照者，对 IL23R 和 IL17A 区域的 23 个 SNP 进行分析。提取基因组 DNA，采用连接酶检测反应等位基因（LDR）技术分析这些 23 个 SNP。采用 SPSS 13.0 软件包计算基因型和等位基因相关性。
与健康对照组相比，IL23R 基因的 rs7530511 和 rs11805303 变异等位基因与溃疡性结肠炎易感性存在统计学差异（0.7%比 3.3%，P=0.002；60.4%比 53.2%，P=0.0017）。对这些 SNP 的连锁不平衡（LD）模式进行了测量，确定了 IL23R 中的三个 SNP 块和 IL17A 中的一个 SNP 块。在 IL23R（Block1 H3，P=0.02；Block2 H2，P=0.019；Block3 H4，P=0.029）和 IL17A（H4，P=0.034）中发现了与溃疡性结肠炎易感性相关的新的单倍型关联。成对分析显示，IL23R 和 IL17A 风险单倍型之间存在相互作用（P=0.014）。
本研究表明，在中国人群中，IL23R 的 rs7530511 和 rs11805303 与溃疡性结肠炎易感性显著相关。最显著的发现是由于基因-基因相互作用，IL23R 和 IL17A 基因区域与溃疡性结肠炎风险相关联。
