血管性水肿患者中激肽生成和生物处置相关遗传变异的检测。
Examination of genetic variants involved in generation and biodisposition of kinins in patients with angioedema.
机构信息
Division of Dermatology and Cutaneous Sciences, University of Alberta, 2-166 Clinical Sciences Building, 11350 - 83 Avenue, Edmonton, Alberta T6G 2G3 Canada.
CHU Sainte-Justine, Université de Montréal, Montreal, QC Canada.
出版信息
Allergy Asthma Clin Immunol. 2014 Dec 12;10(1):60. doi: 10.1186/s13223-014-0060-y. eCollection 2014.
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.
背景
血管性水肿（AE）在大多数情况下是特发性的。我们研究了 AE 患者的血管紧张素转化酶（ACE）抑制剂诱导、非甾体抗炎药（NSAID）诱导、补体 C1 抑制剂（C1-INH）和 C4 水平降低、自身免疫性疾病、癌症等与缓激肽生成和生物分布相关的蛋白的遗传变异。
方法
我们在一家大学医院诊所招募了 161 名 AE 患者。根据 AE 的发病机制，将患者分为以下几类：低 C1 抑制剂（C1-INH）和 C4 水平、自身免疫性疾病、癌症、ACE 抑制剂诱导、非甾体抗炎药（NSAID）诱导或特发性。此外，对每个患者的血液样本进行补体谱和酶（C1-INH 和 C4）分析。对 52 名患者进行了因子 XII、纤溶酶原激活物抑制剂-1（PAI-1）、ACE 和氨肽酶 P（APP）的遗传变异检测。
结果
在 161 例 AE 患者中，59 例（37%）的病因得到了明确：3 例（2%）患者血浆 C1-INH 和 C4 水平低；20 例（12%）为 ACE 抑制剂诱导；12 例（7%）与自身免疫性疾病有关；7 例（4%）与恶性肿瘤有关；17 例（11%）与 NSAID 有关。在其余 102 例（63%）患者中，AE 的病因是特发性的。在 52 例进行基因分析的患者中，13 例（25%）在 APP 中有遗传变异，10 例（19%）在 ACE 中有遗传变异，13 例（25%）在 PAI-1 中有遗传变异，因子 XII 中无遗传变异。
结论
除了相关疾病和药物引起的 AE 外，某些编码与缓激肽生成和/或代谢途径相关蛋白的遗传变异可能与 AE 的发病机制有关。
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