Examination of genetic variants involved in generation and biodisposition of kinins in patients with angioedema
Examination of genetic variants involved in generation and biodisposition of kinins in patients with angioedema
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DOI：
10.1186/s13223-014-0060-y
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发表时间：
2014-12-12
影响因子：
2.7
通讯作者：
Sussman, Gordon L.
中科院分区：
文献类型：
--
作者：
Levy, Jonathan;Rivard, Georges-Etienne;Sussman, Gordon L.
背景：血管水肿(AE)在大多数病例中是特发性的。我们研究了与缓激肽生成和生物分解有关的蛋白的遗传变异。方法：在一所大学医院的诊所收集了161名AE患者。根据已提出的AE的发病机制，将患者分为：低C1INH和C4水平、自身免疫性疾病、癌症、血管紧张素转换酶(ACE)抑制剂诱导的、非类固醇抗炎药物(NSAID)诱导的或特发性。此外，每个患者都进行了补体谱和酶(C1-INH和C4)的血液样本分析。对52例患者进行了凝血因子XII、纤溶酶原激活物抑制物-1(PAI-1)、血管紧张素转换酶(ACE)和氨基肽酶P(APP)基因变异检测。结果：59/161(37%)的患者发现了血管水肿的原因：3(2%)患者的血浆c1-INH和C4水平降低；20(12%)患者由ACE抑制物引起；12(7%)患者与自身免疫性疾病相关；7(4%)患者与恶性肿瘤相关；17(11%)患者与非甾体抗炎相关。在其余102名(63%)患者中，血管性水肿的原因是特发性的。在52例患者中，APP基因变异13例(25%)，ACE基因变异10例(19%)，PAI-1基因变异13例(25%)，FXII基因变异0例(25%)。结论：除相关疾病和药物外，某些编码缓激肽生成和/或分解代谢途径的基因变异可能参与了AE的发病。
Background: Angioedema (AE) is idiopathic in the majority of cases. We studied patients with AE for genetic variants of proteins involved with bradykinin generation and biodisposition.Methods: One hundred sixty one patients with AE were recruited at a university hospital clinic. Patients were categorized according to the proposed pathogenesis of AE: low C1 inhibitor (C1-INH) and C4 levels, autoimmune disease, cancer, angiotensin-converting enzyme (ACE) inhibitor-induced, nonsteroidal antiinflammatory drug (NSAID)-induced, or idiopathic. In addition, each patient had a blood sample analyzed for a complement profile and enzymes (C1-INH and C4). Fifty-two of the patients were tested for genetic variants in factor XII, plasminogen-activator inhibitor-1 (PAI-1), ACE, and aminopeptidase P (APP).Results: The cause of angioedema was identified in 59/161 (37%) of the cases: 3 (2%) patients had a low plasma C1-INH and C4; 20 (12%) were ACE inhibitor-induced; 12 (7%) were associated with autoimmune disorders; 7 (4%) were associated with malignancy; and 17 (11%) were associated with NSAIDs. In the remaining 102 (63%) patients the cause of angioedema was idiopathic. Of 52 patients with genetic analysis, 13 (25%) had a genetic variant in APP, 10 (19%) in ACE, 13 (25%) in PAI-1, and 0 in Factor XII.Conclusions: In addition to related diseases and medications causing AE, certain genetic variants encoding proteins involved in bradykinin generation and/or catabolism pathways may be involved in the pathogenesis of AE.