Institute of Human Genetics, University Hospital Erlangen-Nuremberg, Schwabachanlage 10, 91054 Erlangen, Germany.
Neurosci Lett. 2010 Mar 12;472(1):19-23. doi: 10.1016/j.neulet.2010.01.044. Epub 2010 Jan 25.
Complex regional pain syndrome (CRPS) is a condition that is characterized by severe pain and exaggerated neurogenic inflammation, which may develop after injury or surgery. Neurogenic inflammation is mediated by neuropeptides, such as calcitonin gene-related peptide (CGRP) and substance P (SP) that are released from nociceptors. Genetic factors may play a role in CRPS as was suggested by the occurrence of familial cases and several genetic association studies investigating mainly the human leukocyte antigen (HLA) system. Here we investigated the role of neutral endopeptidase (NEP), a key enzyme in neuropeptide catabolism. NEP dysfunction resulting in reduced inactivation of neuropeptides may be a possible pathomechanism in CRPS. To this end, we tested a GT-repeat polymorphism in the NEP promoter region as well as 18 tag-SNPs in six linkage disequilibrium (LD) blocks in the NEP gene region in 320 CRPS patients and 376 controls. No significant genetic association was observed. Thus, we conclude that the NEP gene does not seem to be a major risk factor for CRPS.
复杂性区域疼痛综合征 (CRPS) 是一种以严重疼痛和夸大的神经源性炎症为特征的疾病，可能在受伤或手术后发展。神经源性炎症由降钙素基因相关肽 (CGRP) 和 P 物质 (SP) 等神经肽介导，这些神经肽从伤害感受器释放。遗传因素可能在 CRPS 中起作用，这一点从家族病例的发生和几项主要研究人类白细胞抗原 (HLA) 系统的遗传关联研究中得到了提示。在这里，我们研究了中性内肽酶 (NEP) 的作用，它是神经肽代谢的关键酶。NEP 功能障碍导致神经肽失活减少可能是 CRPS 的一种潜在病理机制。为此，我们在 320 名 CRPS 患者和 376 名对照中测试了 NEP 启动子区域中的 GT 重复多态性以及 NEP 基因区域中六个连锁不平衡 (LD) 块中的 18 个标记 SNP。未观察到显著的遗传关联。因此，我们得出结论，NEP 基因似乎不是 CRPS 的主要危险因素。
