Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
Gastroenterology, Mayo Clinic Health System, Southwest Minnesota Region, Mankato, Minnesota, USA.
Clin Transl Gastroenterol. 2023 Sep 1;14(9):e00615. doi: 10.14309/ctg.0000000000000615.
Patients with ulcerative colitis (UC) who are likely to have primary sclerosing cholangitis (PSC) should be identified because PSC can influence UC clinical behavior and outcomes.The aim of this study was to establish a model incorporating clinical and genetic risk predictors that identifies patients with UC at risk of developing PSC.
We conducted a retrospective case-control study. Inflammatory bowel disease cohorts from multiple institutions were used as discovery and replicate datasets. Quality control criteria, including minor allele frequency, call rates, Hardy-Weinberg equilibrium, cryptic relatedness, and population stratification (through principal components), were used. Discriminative accuracy was evaluated with area under the receiver operating characteristic curve.
Fifty-seven of 581 patients (9.8%) with UC had PSC. Multivariate analysis showed that patients with UC-PSC had more extensive disease (odds ratio [OR], 5.42; P = 1.57E-04), younger diagnosis age (younger than 20 years; OR, 2.22; P = 0.02), and less smoking (OR, 0.42; P = 0.02) than those with UC. After linkage disequilibrium pruning and multivariate analyses, 3 SNPs (rs3131621 at 6p21.33; rs9275596 and rs11244 at 6p21.32) at the HLA region were found associated with a 2- to 3-fold increased risk of PSC. Our model demonstrated good discriminatory power (area under the receiver operating characteristic curve, 88%).
Three variants in HLA (6p21.3) region significantly distinguished patients with UC-PSC from patients with UC alone. Once further validated in an independent large cohort, our model could be used to identify patients with UC at risk of PSC, and it could also help guide disease management.
患有溃疡性结肠炎（UC）且可能患有原发性硬化性胆管炎（PSC）的患者应被识别，因为 PSC 会影响 UC 的临床行为和结局。本研究旨在建立一个包含临床和遗传风险预测因子的模型，以识别出患有 UC 且有发生 PSC 风险的患者。
我们进行了一项回顾性病例对照研究。来自多个机构的炎症性肠病队列被用作发现和复制数据集。使用了质量控制标准，包括次要等位基因频率、呼叫率、哈迪-温伯格平衡、隐性相关性和群体分层（通过主成分分析）。使用接受者操作特征曲线下的面积来评估判别准确性。
581 例 UC 患者中有 57 例（9.8%）患有 PSC。多变量分析表明，UC-PSC 患者的疾病更广泛（优势比[OR]，5.42；P = 1.57E-04），诊断年龄更年轻（<20 岁；OR，2.22；P = 0.02），吸烟更少（OR，0.42；P = 0.02）。在连锁不平衡修剪和多变量分析后，在 HLA 区域发现 3 个 SNP（rs3131621 在 6p21.33；rs9275596 和 rs11244 在 6p21.32）与 PSC 的 2-3 倍风险增加相关。我们的模型显示出良好的判别能力（接受者操作特征曲线下的面积，88%）。
HLA（6p21.3）区域的三个变体显著区分了 UC-PSC 患者和单纯 UC 患者。一旦在独立的大队列中得到进一步验证，我们的模型可以用于识别患有 UC 且有发生 PSC 风险的患者，也可以帮助指导疾病管理。
