Zotter Zsuzsanna, Nagy Zsolt, Patócs Attila, Csuka Dorottya, Veszeli Nóra, Kőhalmi Kinga Viktória, Farkas Henriette
Hungarian Angioedema Center, 3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi street 4, H-1125, Budapest, Hungary.
Department of Urology, Medical Center, Hungarian Defence Forces, Budapest, Hungary.
Orphanet J Rare Dis. 2017 Jan 10;12(1):5. doi: 10.1186/s13023-016-0552-6.
Hereditary angioedema caused by C1-inhibitor deficiency (C1-INH-HAE) is a rare, autosomal dominant disorder. C1-INH-HAE is characterized by edema-formation, which may occur in response to stress. The individual's response to stress stimuli is partly genetically determined. Activation of the hypothalamic-pituitary-adrenal axis results in the release of cortisol. In turn, the secreted gluco- and mineralocorticoids affect the metabolism, as well as the cardiovascular and immune systems. We hypothesized that changes in serum cortisol level and polymorphisms of the glucocorticoid receptor (GR) modify the individual sensitivity to stressor stimuli of C1-INH-HAE patients.
We compared the response to stress with Rahe's Brief Stress and Coping Inventory of 43 C1-INH-HAE patients, 18 angioedema patients and 13 healthy controls. 139 C1-INH-HAE patients and 160 healthy controls were genotyped for glucocorticoid receptor polymorphisms BclI, N363S and A3669G. Serum cortisol levels were determined during attacks and during symptom-free periods in 36 C1-INH-HAE patients. The relationships between clinical, laboratory data and GR SNPs (Single Nucleotide Polymorphisms) were assessed using ANOVA. C1-INH-HAE patients have decreased coping capabilities compared to healthy controls. Cortisol levels were significantly higher during attacks than in symptom-free periods (p = 0.004). The magnitude of the elevation of cortisol levels did not show a significant correlation with any clinical or laboratory data. Among the C1-INH-HAE patients, the carriers of the A3669G allele had significantly lower cortisol levels, and increased body mass index compared with non-carriers.
The higher cortisol level observed during attacks may reflect the effect of a stressful situation (such as of the attack itself), on the patients' neuroendocrine system. In A3669G carriers, the lower cortisol levels might reflect altered feedback to the hypothalamic-pituitary-adrenal axis, due to decreased sensitivity to glucocorticoids.
C1抑制物缺乏所致遗传性血管性水肿（C1-INH-HAE）是一种罕见的常染色体显性疾病。C1-INH-HAE的特征是水肿形成，可能因应激而发生。个体对应激刺激的反应部分由基因决定。下丘脑-垂体-肾上腺轴的激活导致皮质醇释放。反过来，分泌的糖皮质激素和盐皮质激素会影响新陈代谢以及心血管和免疫系统。我们假设血清皮质醇水平的变化和糖皮质激素受体（GR）的多态性会改变C1-INH-HAE患者对应激源刺激的个体敏感性。
我们使用拉赫简易应激与应对量表比较了43例C1-INH-HAE患者、18例血管性水肿患者和13例健康对照对应激的反应。对139例C1-INH-HAE患者和160例健康对照进行了糖皮质激素受体多态性BclI、N363S和A3669G的基因分型。测定了36例C1-INH-HAE患者发作期间和无症状期的血清皮质醇水平。使用方差分析评估临床、实验室数据与GR单核苷酸多态性（SNP）之间的关系。与健康对照相比，C1-INH-HAE患者的应对能力下降。发作期间的皮质醇水平显著高于无症状期（p = 0.004）。皮质醇水平升高的幅度与任何临床或实验室数据均无显著相关性。在C1-INH-HAE患者中，A3669G等位基因携带者的皮质醇水平显著低于非携带者，且体重指数增加。
发作期间观察到的较高皮质醇水平可能反映了应激情况（如发作本身）对患者神经内分泌系统的影响。在A3669G携带者中，较低的皮质醇水平可能反映了由于对糖皮质激素敏感性降低，下丘脑-垂体-肾上腺轴的反馈改变。
