Division of Therapeutics and Molecular Medicine, University of Nottingham, Nottingham, UK.
Gut. 2013 Jul;62(7):985-94. doi: 10.1136/gutjnl-2011-301213. Epub 2012 Jun 8.
The postinfectious irritable bowel syndrome (PI-IBS) suggests that impaired resolution of inflammation could cause IBS symptoms. The authors hypothesised that polymorphisms in genes whose expression were altered by gastroenteritis might be linked to IBS with diarrhoea (IBS-D) which closely resembles PI-IBS.
Part 1: 25 healthy volunteers (HVs), 21 patients 6 months after Campylobacter jejuni infection, 37 IBS-D and 19 IBS with constipation (IBS-C) underwent rectal biopsy for gene expression analysis and peripheral blood mononuclear cell cytokine production assessment. Part 2: Polymorphisms in genes whose expression was altered in Part 1 were assessed in 179 HV, 179 IBS-D, 122 IBS-C and 41 PI-IBS.
Part 1: Mucosal expression of seven genes was altered in IBS: CCL11, CCL13, Calpain 8 and TNFSF15 increased while NR1D1, GPR161 and GABRE decreased with similar patterns after infection with C jejuni. Part 2: The authors assessed 21 known single nucleotide polymorphisms (SNPs) in these seven genes and one SNP in each of the TNFα and IL-10 genes. Three out of five TNFSF15 SNPs (rs6478108, rs6478109 and rs7848647) showed reduced minor allele frequency (MAF) (0.28, 0.27 and 0.27) in subjects with IBS-D compared with HV (0.38, 0.36 and 0.37; p=0.007, 0.015 and 0.007, respectively) confirming others recent findings. The authors also replicated the previously reported association of the TNFα SNP rs1800629 with PI-IBS which showed an increase in the MAF at 0.30 versus 0.19 for HV (p=0.04).
IBS-D and PI-IBS patients are associated with TNFSF15 and TNFα genetic polymorphisms which also predispose to Crohn's disease suggesting possible common underlying pathogenesis.
感染后肠易激综合征（PI-IBS）表明炎症的消退受损可能导致 IBS 症状。作者假设，其表达受肠胃炎改变的基因的多态性可能与类似 PI-IBS 的腹泻型肠易激综合征（IBS-D）有关。
第 1 部分：25 名健康志愿者（HV）、21 名感染空肠弯曲菌 6 个月后的患者、37 名 IBS-D 和 19 名 IBS 伴便秘（IBS-C）进行直肠活检，进行基因表达分析和外周血单个核细胞细胞因子产生评估。第 2 部分：评估第 1 部分中表达改变的基因中的多态性，在 179 名 HV、179 名 IBS-D、122 名 IBS-C 和 41 名 PI-IBS 中进行。
第 1 部分：在感染空肠弯曲菌后，IBS 中七种基因的粘膜表达发生改变：CCL11、CCL13、钙蛋白酶 8 和 TNFSF15 增加，而 NR1D1、GPR161 和 GABRE 减少，具有相似的模式。第 2 部分：作者评估了这七个基因中的 21 个已知单核苷酸多态性（SNP）和 TNFα 和 IL-10 基因中的每个基因中的一个 SNP。TNFSF15 基因的五个 SNP 中的三个（rs6478108、rs6478109 和 rs7848647）在 IBS-D 患者中显示出较小的等位基因频率（MAF）（0.28、0.27 和 0.27），低于 HV（0.38、0.36 和 0.37；p=0.007、0.015 和 0.007，分别）证实了其他人最近的发现。作者还复制了 TNFα SNP rs1800629 与 PI-IBS 的先前报道的关联，该关联显示 MAF 在 0.30 处增加，而 HV 为 0.19（p=0.04）。
IBS-D 和 PI-IBS 患者与 TNFSF15 和 TNFα 遗传多态性相关，这些多态性也易患克罗恩病，表明可能存在共同的潜在发病机制。
