Santos Marlene, Carvalho Serafim, Lima Luís, Mota-Pereira Jorge, Pimentel Paulo, Maia Dulce, Correia Diana, Gomes Sofia, Cruz Agostinho, Medeiros Rui
Molecular Oncology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology, Porto, Portugal; Núcleo de Investigação e Informação em Farmácia-Centro de Investigação em Saúde e Ambiente (CISA), School of Allied Health Technologies, Polytechnic Institute of Porto, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal.
Hospital de Magalhães Lemos, Porto, Portugal; Instituto Superior de Ciências da Saúde, Norte, Portugal.
Neurosci Lett. 2016 May 27;622:107-12. doi: 10.1016/j.neulet.2016.03.026. Epub 2016 Mar 18.
Recent studies suggest that immune activation and cytokines, such as IL-18, are involved in depression. IL-18 is expressed in brain and is increased in patients with moderate to severe depression. In this study we aim to evaluate the role of IL18-607C>A and IL18-137G>C promoter polymorphisms in antidepressant treatment phenotypes, specifically relapse and treatment resistant depression (TRD). We genotyped the referred polymorphisms in a subset of 80 MDD patients followed at Hospital Magalhães Lemos, Portugal, within a period of 27 months. Patients carrying IL18-607 CA or AA genotypes were significantly more prone to relapse after AD treatment and present a significantly lower time to relapse than patients carrying CC genotype. Similarly, patients carrying IL18-137 GC or CC genotypes have a significantly higher risk of relapse and display relapse significantly earlier than the ones carrying GG genotype. Due to the low number of IL18-607 CC and IL18-137 GG in the relapse subgroup (n=3 and n=5, respectively), results were validated by bootstrapping analysis, and remained significant. No association was found between the evaluated genetic polymorphisms and TRD. IL18 peripheral mRNA levels were upregulated in IL18-607 CA or AA carriers. This preliminary report indicates that IL18-607C>A and IL18-137G>C genetic polymorphisms seem to influence depression relapse after antidepressant treatment in our subset of depressed patients, and may possibly contribute to the disregulated IL-18 levels found in patients with depression.
最近的研究表明，免疫激活和细胞因子，如白细胞介素-18（IL-18），与抑郁症有关。IL-18在大脑中表达，在中度至重度抑郁症患者中升高。在本研究中，我们旨在评估IL18-607C>A和IL18-137G>C启动子多态性在抗抑郁治疗表型中的作用，特别是复发和治疗抵抗性抑郁症（TRD）。我们对葡萄牙马加良斯·莱莫斯医院随访的80例重度抑郁症（MDD）患者在27个月内的上述多态性进行了基因分型。携带IL18-607 CA或AA基因型的患者在抗抑郁治疗后复发的可能性明显更高，且复发时间明显短于携带CC基因型的患者。同样，携带IL18-137 GC或CC基因型的患者复发风险明显更高，且复发时间明显早于携带GG基因型的患者。由于复发亚组中IL18-607 CC和IL18-137 GG的数量较少（分别为n = 3和n = 5），结果通过自抽样分析进行了验证，且仍然具有显著性。在评估的基因多态性与TRD之间未发现关联。IL18外周mRNA水平在IL18-607 CA或AA携带者中上调。这份初步报告表明，IL18-607C>A和IL18-137G>C基因多态性似乎会影响我们这组抑郁症患者抗抑郁治疗后的抑郁症复发，并且可能导致抑郁症患者中发现的IL-18水平失调。
