The diamine oxidase gene is associated with hypersensitivity response to non-steroidal anti-inflammatory drugs.
The diamine oxidase gene is associated with hypersensitivity response to non-steroidal anti-inflammatory drugs.
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DOI：
10.1371/journal.pone.0047571
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
García-Martín E
中科院分区：
文献类型：
--
作者：
Agúndez JA;Ayuso P;Cornejo-García JA;Blanca M;Torres MJ;Doña I;Salas M;Blanca-López N;Canto G;Rondon C;Campo P;Laguna JJ;Fernández J;Martínez C;García-Martín E
非甾体抗炎药（NSAID）是最常引起药物超敏反应的药物。组胺在对NSAID的过敏反应中释放，并导致一些临床症状。本研究的目的是分析编码组胺稳态相关酶的基因的功能多态性与NSAID过敏反应的临床相关性。我们研究了442例对NSAID过敏的无关白人患者。包括使用两种或更多种不同NSAID发生三次或更多次发作的患者。如果不符合该要求，则通过攻毒确定诊断。共招募了414名与患者种族匹配且来自同一地理区域的健康无关对照。通过TaqMan分析法对HDC、HNMT和DAO基因中的SNPs rs 17740607、rs 2073440、rs 1801105、rs 2052129、rs 10156191、rs 1049742和rs 1049793进行分析。导致代谢能力下降的有害DAO 16 Met等位基因（rs 10156191）在对NSAID交叉过敏的患者中比例过高，OR = 1.7（95%CI = 1.3-2.1; Pc = 0.0003），具有基因剂量效应（P = 0.0001）。 这种关联在来自不同地理区域的两个群体中重复（分别为Pc= 0.008和Pc =0.004）。 DAO基因多态性rs 10156191导致循环组胺代谢受损，与NSAID交叉超敏反应的临床反应相关，可作为反应的生物标志物。
Non-steroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in hypersensitivity drug reactions. Histamine is released in the allergic response to NSAIDs and is responsible for some of the clinical symptoms. The aim of this study is to analyze clinical association of functional polymorphisms in the genes coding for enzymes involved in histamine homeostasis with hypersensitivity response to NSAIDs. We studied a cohort of 442 unrelated Caucasian patients with hypersensitivity to NSAIDs. Patients who experienced three or more episodes with two or more different NSAIDs were included. If this requirement was not met diagnosis was established by challenge. A total of 414 healthy unrelated controls ethnically matched with patients and from the same geographic area were recruited. Analyses of the SNPs rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742 and rs1049793 in the HDC, HNMT and DAO genes were carried out by means of TaqMan assays. The detrimental DAO 16 Met allele (rs10156191), which causes decreased metabolic capacity, is overrepresented among patients with crossed-hypersensitivity to NSAIDs with an OR = 1.7 (95% CI = 1.3–2.1; Pc = 0.0003) with a gene-dose effect (P = 0.0001). The association was replicated in two populations from different geographic areas (Pc = 0.008 and Pc = 0.004, respectively). The DAO polymorphism rs10156191 which causes impaired metabolism of circulating histamine is associated with the clinical response in crossed-hypersensitivity to NSAIDs and could be used as a biomarker of response.
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影响因子：
3.6
作者：
Preuss, CV;Wood, TC;Weinshilboum, RM
通讯作者：
Weinshilboum, RM
影响因子：
4.3
作者：
Garcia-Martin, Elena;Mendoza, Juan L.;Agundez, Jose A. G.
通讯作者：
Agundez, Jose A. G.
影响因子：
4.1
作者：
Kennedy, Mary Jayne;Loehle, Jennifer A.;Hein, David W.
通讯作者：
Hein, David W.
影响因子：
12.4
作者：
Gervasini, G.;Agundez, J. A. G.;Garcia-Martin, E.
通讯作者：
Garcia-Martin, E.
影响因子：
14.2
作者：
Khan, David A.;Solensky, Roland
通讯作者：
Solensky, Roland