Tumor necrosis factor receptor gene polymorphisms in Crohn's disease: Association with clinical phenotypes
Tumor necrosis factor receptor gene polymorphisms in Crohn's disease: Association with clinical phenotypes
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DOI：
10.1111/j.1572-0241.2005.40534.x
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发表时间：
2005-05-01
影响因子：
9.8
通讯作者：
Wild, GE
中科院分区：
文献类型：
--
作者：
Waschke, KA;Villani, AC;Wild, GE
目的：克罗恩病(CD)是一种慢性多因素疾病，临床表现多样，受多种遗传因素影响。肿瘤坏死因子-α/肿瘤坏死因子受体的相互作用在炎症反应的发病机制中起着关键作用。我们的目的是确定肿瘤坏死因子受体的单核苷酸多态(SNPs)是否增加克罗恩病的易感性，以及它们是否与临床表型相关。方法：纳入205例连续确诊的CD患者和106例对照。受试者接受了TNFRSF1A(位置+36，-609)、TNFRSF1B(+196，+1466)以及三个常见的CARD15变异的基因分型，并对疾病行为进行了表型分析。结果：只有TNFRSF1a+36和TNFRSF1B+196SNPs与CD相关(p分别为0.0019和0.034)。TNFRSF1a+36突变与狭窄病变表型呈负相关(OR=0.384；CI=0.166~0.887)。相反，TNFRSF1B+196与结肠炎呈负相关(OR=0.410；CI=0.191~0.880)。这些关联与CARD15突变状态无关。最后，在CARD15阴性患者中，TNFRSF1B+196与手术负相关。结论：这些数据构成了在高加索人群中TNFRSF1A和TNFRSF1B多态与CD关联的第一个报告，并说明了TNFR突变在确定CD临床异质性中的作用。
OBJECTIVES: Crohn's disease (CD) is a chronic multifactorial disorder with diverse clinical features that are influenced by a heterogeneous set of genetic factors. TNF-alpha/TNF receptor interactions play a pivotal role in the pathogenesis of the inflammatory response. Our purpose was to determine whether single nucleotide polymorphisms (SNPs) in the TNF receptors confer susceptibility to Crohn's disease and whether they are associated with clinical phenotype.METHODS: A cohort of 205 consecutively identified and unrelated patients with CD and 106 controls were recruited. Subjects were genotyped for polymorphisms in TNFRSF1A (position +36, -609), TNFRSF1B (+196, +1466), along with the three common CARD15 variants and phenotyped for disease behavior. Genotypic and allelic frequencies were compared between CD and controls and a logistic regression model was constructed to determine independent associations with specific clinical phenotypes.RESULTS: Only the TNFRSF1A +36 and TNFRSF1B +196 SNPs were associated with CD (p = 0.0019 and 0.034, respectively). The TNFRSF1A +36 mutation was negatively associated with stricturing disease phenotype (OR = 0.384; CI = 0.166-0.887). In contrast, the TNFRSF1B +196 was negatively associated with colitis (OR = 0.410; CI = 0.191-0.880). These associations were independent of CARD15 mutation status. Finally, TNFRSF1B +196 was negatively associated with surgery in CARD15 negative patients.CONCLUSIONS: These data constitute the first report of an association of TNFRSF1A and TNFRSF1B polymorphisms with CD in a Caucasian population and address the role of TNFR mutations in determining clinical heterogeneity in CD.