Talaei Ali, Tavakkol Afshari Jalil, Fayyazi Bordbar Mohammad Reza, Pouryousof Hamidreza, Faridhosseini Farhad, Saghebi Ali, Rezaei Ardani Amir, Talaei Andisheh, Tehrani Mohsen
Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Allergy Asthma Immunol. 2016 Dec;15(6):466-475.
The pathogenesis of Bipolar I Disorder (BP-I) involves immune-mediated mechanisms, especially an imbalance in pro-inflammatory/anti-inflammatory cytokines in plasma or cerebrospinal fluid. Interleukin-1 (IL-1) gene cluster, coding some of these pro-inflammatory cytokines, might play a role in various neuropathologies related to neuron inflammation. The aim of the present study was to investigate the possible role of IL-1 gene cluster polymorphisms in determining the susceptibility to BP-I in Iranian population. 48 patients with BP-I in Mashhad (in north-eastern Iran), diagnosed by two psychiatrists using SCID (structured clinical interview for DSM disorders) were selected through convenient sampling and were compared with 47 healthy controls, voluntarily enrolled in the study. Patients with non-Persian ethnicity, history of immunoallergic disorders, endocrinopathies, neurologic disorders, and substance-induced mood disorders were excluded from both case and control groups. Genotyping of IL-1 gene cluster polymorphisms, including IL-1a-889, IL-1b +3954, IL-1b-511, and IL-1RN (VNTR) were carried out using Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and compared by SPSS using Fisher's exact and chi-square tests. The frequency of IL-1b-511 CC genotype and C/T allelic frequency were significantly different between BMD patients and healthy controls (p=0.04 and p=0.02, respectively). Among patients, -511 T allele was significantly more frequent in those with a positive history of major depression. Moreover, +3954 T allele was significantly more frequent in early onset BMD patients. The results suggest a positive association between IL-1 gene cluster variation and BP-I. This polymorphism may contribute to genetic vulnerability through its possible role in neuron inflammation.
双相I型障碍（BP-I）的发病机制涉及免疫介导机制，尤其是血浆或脑脊液中促炎/抗炎细胞因子的失衡。白细胞介素-1（IL-1）基因簇编码其中一些促炎细胞因子，可能在与神经元炎症相关的各种神经病理学中起作用。本研究的目的是调查IL-1基因簇多态性在伊朗人群中确定BP-I易感性方面的可能作用。通过便利抽样，选择了48例来自伊朗东北部马什哈德的BP-I患者，由两名精神科医生使用DSM障碍的结构化临床访谈（SCID）进行诊断，并与47名自愿参与研究的健康对照进行比较。病例组和对照组均排除非波斯族裔、免疫过敏疾病史、内分泌疾病、神经系统疾病和物质所致情绪障碍患者。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对IL-1基因簇多态性进行基因分型，包括IL-1a -889、IL-1b +3954、IL-1b -511和IL-1RN（VNTR），并使用SPSS通过Fisher精确检验和卡方检验进行比较。BP-I患者和健康对照之间IL-1b -511 CC基因型频率和C/T等位基因频率存在显著差异（分别为p = 0.04和p = 0.02）。在患者中，有重度抑郁阳性病史者中-511 T等位基因频率显著更高。此外，早发性BP-I患者中+3954 T等位基因频率显著更高。结果表明IL-1基因簇变异与BP-I之间存在正相关。这种多态性可能通过其在神经元炎症中的可能作用导致遗传易感性。
