Variability of the L-Histidine decarboxylase gene in allergic rhinitis
Variability of the L-Histidine decarboxylase gene in allergic rhinitis
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DOI：
10.1111/j.1398-9995.2010.02425.x
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发表时间：
2010-12-01
期刊：
影响因子：
12.4
通讯作者：
Garcia-Martin, E.
中科院分区：
文献类型：
--
作者：
Gervasini, G.;Agundez, J. A. G.;Garcia-Martin, E.
背景：组胺代谢酶、二胺氧化酶和组胺n -甲基转移酶基因编码的非同义多态性与过敏性疾病的发生风险有关。组氨酸脱羧酶基因多态性的作用仍未被探索。本研究的目的是鉴定人类组氨酸脱羧酶基因的新多态性，并分析非同义多态性与鼻炎的临床关联。方法：对组氨酸脱羧酶基因序列进行单链构象多态性分析。在442例不相关的变应性鼻炎患者（其中233例同时患有哮喘）和486例健康受试者中分析了两个非同义多态性Thr31Met （rs17740607）和Glu644Asp （rs2073440）的存在。结果：我们发现了3个新的多态性，分别为ss50402829、ss50402830和ss50402831-(rs17740607)，等位基因频率分别为- 0.005、0.208和0.073。组氨酸脱羧酶Glu644Asp （rs2073440）多态性差异有统计学意义，与健康对照组相比，Glu644等位基因纯合携带者的OR （95% CI）值为3.12 (1.75 ~ 5.56,P < 0.00005)，鼻炎患者的OR （95% CI）值为3.38 (1.54 ~ 7.44,P = 0.002)，鼻炎+哮喘患者的OR （95% CI）值为2.92 (1.43 ~ 5.95),P = 0.003。在整体患者（P = 0.0001）、单独鼻炎患者（P = 0.005）和鼻炎+哮喘患者（P = 0.010）中观察到显著的Glu644基因剂量效应。结论：HDC等位基因Glu644的纯合性增加了研究人群发生鼻炎的风险。这增加了越来越多的证据，支持与组胺稳态相关的遗传变异在过敏性疾病发生风险中的突出作用。
Background: Nonsynonymous polymorphisms in genes coding for histamine-metabolizing enzymes, diamine oxidase and histamine N-methyltransferase are related to the risk of developing allergic diseases. The role of polymorphisms in the histidine decarboxylase gene remains unexplored. The objective of this study is to identify novel polymorphisms in the human histidine decarboxylase gene and to analyse the clinical association of nonsynonymous polymorphisms with rhinitis.Methods: We performed a single-strand conformational polymorphism analysis of the histidine decarboxylase gene sequence. The presence of two nonsynonymous polymorphisms Thr31Met (rs17740607) and Glu644Asp (rs2073440) was analysed in 442 unrelated patients with allergic rhinitis, 233 of whom also had asthma, and in 486 healthy subjects.Results: We observed three novel polymorphisms designated as ss50402829, ss50402830 and ss50402831-(rs17740607) with allele frequencies - 0.005, 0.208 and 0.073, respectively. Statistically significant differences were observed for the histidine decarboxylase Glu644Asp (rs2073440) polymorphism, with OR (95% CI) values for homozygous carriers of the Glu644 allele equal to 3.12 (1.75-5.56, P < 0.00005) for all patients, 3.38 (1.54-7.44, P = 0.002) for patients with rhinitis alone, and 2.92 (1.43 5.95), P = 0.003 for patients with rhinitis + asthma, when compared with healthy controls. A significant Glu644 gene-dose effect was observed for overall patients (P = 0.0001), for patients with rhinitis alone (P = 0.005) and for patients with rhinitis + asthma (P = 0.010).Conclusions: The HDC allele Glu644 in homozygosity increases the risk of developing rhinitis in the studied population. This adds to increasing evidence supporting a prominent role of genetic variations related to histamine homeostasis in the risk to develop allergic diseases.