Severity of ulcerative colitis is associated with a polymorphism at diamine oxidase gene but not at histamine N-methyltransferase gene
Severity of ulcerative colitis is associated with a polymorphism at diamine oxidase gene but not at histamine N-methyltransferase gene
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DOI：
10.3748/wjg.v12.i4.615
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发表时间：
2006-01-28
影响因子：
4.3
通讯作者：
Agundez, Jose A. G.
中科院分区：
文献类型：
--
作者：
Garcia-Martin, Elena;Mendoza, Juan L.;Agundez, Jose A. G.
目的：分析编码组胺代谢酶的基因中两种常见多态性的作用，因为它与溃疡性结肠炎（UC）的发生风险和这些患者的临床病程有关。分析了从一个中心招募的229名不相关的UC患者和261名健康志愿者的队列中组胺N-端Thr 105 Ile和His 645 Asp氨基酸置换的存在。甲基转移酶（HNMT）和二胺氧化酶（ABP 1）酶。结果：溃疡性结肠炎患者与健康对照组ABP 1等位基因分布差异无统计学意义[变异等位基因OR（95%CI）= 1.22（0.91-1.61）]。然而，突变的ABP 1等位基因在58例需要免疫抑制剂的患者中以更高的频率存在[突变等位基因携带者的OR（95%CI）为2.41（1.21-4.83; P = 0.006）]，具有显著的基因剂量效应（P = 0.0038）。在协议中的主要作用，ABP 1与HNMT对局部组胺代谢在人体肠道，HNMT基因型或突变等位基因的携带者的频率是相似的患者之间，无论临床演变，和对照individual.CONCLUSION：组胺代谢酶ABP 1的His 645 Asp多态性与溃疡性结肠炎的严重程度。(C)2006年，WJG出版社。All rights reserved.
AIM: To analyse the role of two common polymorphisms in genes coding for histamine metabolising enzymes as it relates to the risk to develop ulcerative colitis (UC) and the clinical course of these patients.METHODS: A cohort of 229 unrelated patients with UC recruited from a single centre and 261 healthy volunteers were analysed for the presence of Thr105Ile and His645Asp amino acid substitutions at histamine N-methyltransferase (HNMT) and diamine oxidase (ABP1) enzymes, respectively, by amplification-restriction procedures. All patients were phenotyped and followed up for at least 2 years (mean time 11 years).RESULTS: There were no significant differences in the distribution of ABP1 alleles between ulcerative colitis patients and healthy individuals [OR (95% CI) for variant alleles = 1.22 (0.91-1.61)]. However, mutated ABP1 alleles were present with higher frequency among the 58 patients that required immunosuppresive drugs [OR (95% CI) for carriers of mutated alleles 2.41 (1.21-4.83; P = 0.006)], with a significant gene-dose effect (P = 0.0038). In agreement with the predominant role of ABP1 versus HNMT on local histamine metabolism in human bowel, the frequencies for carriers of HNMT genotypes or mutated alleles were similar among patients, regardless clinical evolution, and control individuals.CONCLUSION: The His645Asp polymorphism of the histamine metabolising enzyme ABP1 is related to severity of ulcerative colitis. (C) 2006 The WJG Press. All rights reserved.