Yang W, Yang S X, Xu C L, Yu L M, Lin H, Jiang Y
Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Zhonghua Nei Ke Za Zhi. 2018 Jul 1;57(7):476-482. doi: 10.3760/cma.j.issn.0578-1426.2018.07.002.
To explore the relationship between ulcerative colitis (UC) susceptibility and tumor necrosis factor superfamily member (TNFSF) 15 gene polymorphisms and haplotypes in Han nationality in Zhejiang province of China. A total of 408 UC patients and 574 healthy controls were recruited in this study. Three single nucleotide polymorphisms of TNFSF15 (rs3810936, rs4263839, rs4979462) were examined by improved multiple ligase detection reaction (iMLDR) technique. Analyses of linkage disequilibrium (LD) and haplotype were performed by Haploview 4.2 software in all study subjects. The variant allele A and genotype (GA+AA) of rs4263839 were less frequent in UC patients than in controls (45.34% vs. 50.17%, 0.035;68.38% vs. 76.66%, 0.004). According to the severity and location of disease, UC patients were divided into different subgroups. After multiple comparison correction(α=0.012 5), the frequencies of variant allele A and genotype (GA+AA) of rs4263839 were lower in patients with severe UC than in the controls (37.69% vs. 50.17%, 0.007; 60.00% vs. 76.66%, 0.004). Similar findings were also drawn for patients with extensive colitis in contrast with the controls (42.22% vs. 50.17%, 0.009; 63.33% vs. 76.66%, 0.001). Furthermore, the haplotype analysis indicated that three SNPs above were in a strong LD. The frequency of haplotype TAC was lower in UC patients than in the controls(40.83% vs. 46.04%, 0.023). Also it was less prevalent in patients with severe UC and patients with extensive colitis when compared with controls respectively (33.38% vs. 46.04%, 0.005;37.22% vs. 46.04%, 0.003). TNFSF15 (rs4263839) variation might not only reduce the risk of UC, but also affect the severity and lesion location of UC. The haplotype TAC formed by rs3810936, rs4263839 and rs4979462 might be related to a lower risk of UC, especially in patients with severe colitis or patients with extensive colitis.
为探讨中国浙江省汉族人群中溃疡性结肠炎（UC）易感性与肿瘤坏死因子超家族成员（TNFSF）15基因多态性及单倍型的关系。本研究共纳入408例UC患者和574例健康对照。采用改良多重连接酶检测反应（iMLDR）技术检测TNFSF15的3个单核苷酸多态性（rs3810936、rs4263839、rs4979462）。运用Haploview 4.2软件对所有研究对象进行连锁不平衡（LD）分析和单倍型分析。rs4263839的变异等位基因A及基因型（GA+AA）在UC患者中的频率低于对照组（45.34%对50.17%，P=0.035；68.38%对76.66%，P=0.004）。根据疾病的严重程度和部位，将UC患者分为不同亚组。经多重比较校正（α=0.012 5）后，rs4263839的变异等位基因A及基因型（GA+AA）在重度UC患者中的频率低于对照组（37.69%对50.17%，P=0.007；60.00%对76.66%，P=0.004）。广泛性结肠炎患者与对照组相比也有类似结果（42.22%对50.17%，P=0.009；63.33%对76.66%，P=0.001）。此外，单倍型分析表明上述3个单核苷酸多态性处于强连锁不平衡状态。UC患者中单倍型TAC的频率低于对照组（40.83%对46.04%，P=0.023）。与对照组相比，其在重度UC患者和广泛性结肠炎患者中也分别较少见（33.38%对46.04%，P=0.005；37.22%对46.04%，P=0.003）。TNFSF15（rs4263839）变异可能不仅降低UC发病风险，还会影响UC的严重程度及病变部位。由rs3810936、rs4263839和rs4979462构成的单倍型TAC可能与较低的UC发病风险相关，尤其在重度结肠炎患者或广泛性结肠炎患者中。
