Roberts Rebecca L, Wallace Mary C, Harrison Andrew A, White Douglas, Dalbeth Nicola, Stamp Lisa K, Ching Daniel, Highton John, Merriman Tony R, Robinson Philip C, Brown Matthew A, Stebbings Simon M
Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Department of Medicine, University of Otago Wellington, Wellington, New Zealand.
PeerJ. 2018 Jun 26;6:e5088. doi: 10.7717/peerj.5088. eCollection 2018.
Genome-wide association studies have identified a plethora of risk genes for both Crohn's disease (CD) and ankylosing spondylitis (AS). A subset of genes found to be risk factors for CD have also been found to be risk factors for AS. The objective of our study was to assess whether CD risk genes were associated with non-invasive clinical markers of gut inflammation in patients with AS, indicating a potential subset of patients with clinical as well as genetic overlap.
A total of 308 Caucasian patients who fulfilled the modified New York Criteria for AS, were assessed for bowel symptoms using the Dudley Inflammatory Bowel Symptom Questionnaire (DISQ). Of these patients, 157 also had faecal calprotectin measured. All AS patients and 568 healthy controls were genotyped for 10 CD risk loci using predesigned single nucleotide polymorphism (SNP) genotyping assays. Chi-square analysis was used to test for association between genotype and DISQ score and faecal calprotectin level.
The minor allele of two SNPs, one in chromosome region 1q32 SNP (rs11584383), and one in the gene coding for (rs11209026) conferred protection against AS. Only the association of 1q32 remained significant after Bonferroni correction for multiple testing. Stratification by DISQ score and faecal calprotectin did not influence the association of 1q32 with AS.
In patients with AS, the association of the CD 1q32 SNP was independent of non-invasive markers of bowel inflammation. Other CD related SNPs were not found have a significant association with AS.
全基因组关联研究已经确定了大量克罗恩病（CD）和强直性脊柱炎（AS）的风险基因。已发现一部分基因既是CD的风险因素，也是AS的风险因素。我们研究的目的是评估CD风险基因是否与AS患者肠道炎症的非侵入性临床标志物相关，这表明可能存在临床和基因重叠的患者亚组。
共有308名符合修订的纽约AS标准的白种人患者，使用达德利炎症性肠病症状问卷（DISQ）评估肠道症状。在这些患者中，157人还检测了粪便钙卫蛋白。使用预先设计的单核苷酸多态性（SNP）基因分型检测法，对所有AS患者和568名健康对照进行10个CD风险位点的基因分型。采用卡方分析来检验基因型与DISQ评分及粪便钙卫蛋白水平之间的关联。
两个SNP的次要等位基因，一个位于染色体区域1q32 SNP（rs11584383），另一个位于编码[此处原文缺失基因名]的基因中（rs11209026），对AS具有保护作用。在进行多重检验的Bonferroni校正后，只有1q32的关联仍然显著。按DISQ评分和粪便钙卫蛋白分层并不影响1q32与AS的关联。
在AS患者中，CD 1q32 SNP的关联与肠道炎症的非侵入性标志物无关。未发现其他与CD相关的SNP与AS有显著关联。
