Role of TNFRSF1B polymorphisms in the response of Crohn's disease patients to infliximab
Role of TNFRSF1B polymorphisms in the response of Crohn's disease patients to infliximab
复制标题
DOI：
10.1016/j.humimm.2013.09.017
复制
发表时间：
2014-01-01
期刊：
影响因子：
2.7
通讯作者：
Nunez, C.
中科院分区：
文献类型：
--
作者：
Medrano, L. M.;Taxonera, C.;Nunez, C.
英夫利昔单抗（IFX）是克罗恩病（CD）的有效治疗方法，但相关百分比的患者无法从该治疗中获益。在日本人群中，对IFX的应答与TNF受体超家族1A（TNFRSF 1A）和I B（TNFRSF 1B）基因中的标志物相关。我们的目的是复制先前在日本人群中描述的关联，并确定TNF受体作为IFX反应调节剂的作用。我们研究了297例已知对IFX有应答的白色西班牙CD患者：238例应答者和59例主要无应答者。分析了4种单核苷酸多态性（SNP）：TNFRSF 1A中的rs767455和TNFRSF 1B中的rs 1061622、rs 1061624和rs3397。组间比较采用卡方检验或Fisher精确检验。不同的特征（性别、年龄、病程、吸烟等）被评估为可能的混杂因素。在所研究的TNFRSF 1A多态性和IFX反应之间没有发现显著关联。在TNFRSF 1B基因中，单倍型rs 1061624_A-rs3397_T在无应答者中显著增加：p = 0.015，OR = 1.78，95%CI 1.09- 2.90;在缓解患者中观察到rs1061622_G携带者的频率增加：p = 0.033 vs无应答者，p = 0.023 vs部分应答患者。我们的研究结果支持TNFRSF 1B基因变异体在CD患者对IFX反应中的作用。(C)2013年美国组织相容性和免疫遗传学学会。爱思唯尔公司出版All rights reserved.
Infliximab (IFX) is a valid treatment for Crohn's disease (CD), but a relevant percentage of patients do not benefit from this therapy. In the Japanese population, the response to IFX was associated with markers in the TNF receptor superfamily 1A (TNFRSF1A) and I B (TNFRSF1B) genes. We aimed to replicate the association previously described in the Japanese population and to ascertain the role of TNF receptors as modulators of the response to IFX. We studied 297 white Spanish CD patients with a known response to IFX: 238 responders and 59 primary nonresponders. Four single nucleotide polymorphisms (SNPs) were analyzed: rs767455 in TNFRSF1A and rs1061622, rs1061624, and rs3397 in TNFRSF1B. Comparisons between groups were performed with chi-square tests or the Fisher's exact test. Different features (sex, age, disease duration, smoking among others) were evaluated as possible confounding factors. No significant association was found between the studied TNFRSF1A polymorphisms and response to IFX. In the TNFRSF1B gene, the haplotype rs1061624_A-rs3397_T was significantly increased in nonresponders: p = 0.015, OR = 1.78, 95% CI 1.09- 2.90; and an increased frequency of rs1061622_G carriers was observed in patients with remission: p = 0.033 vs nonresponders and p = 0.023 vs patients with a partial response. Our results support a role of TNFRSF1B gene variants in the response to IFX in CD patients. (C) 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.