Ozbey Ulku, Tug Esra, Kara Murat, Namli Mustafa
Firat University, Faculty of Medicine, Department of Medical Biology and Genetics, Elazig, Turkey.
Psychiatry Clin Neurosci. 2008 Jun;62(3):307-12. doi: 10.1111/j.1440-1819.2008.01798.x.
It has been hypothesized that the activation of the immune system may be involved in the neuropathological changes occurring in the central nervous system of schizophrenic patients. Cytokines play a key role in the activation of the immune system. Moreover, they strongly influence the dopaminergic, noradrenergic and serotonergic neurotransmission. To the best of our knowledge, in schizophrenic patients, plasma levels of interleukin (IL)-12 were investigated only in one study, where deregulation of IL-12 was determined. However, genotypical variations of the IL-12B (p40) gene have not been investigated for schizophrenic patients yet. Therefore, in the present study, we aimed to examine polymorphic variants of IL-12B (p40) gene promoter region in patients with schizophrenia in a population of the Elazig Region of East Anatolia, Turkey.
One hundred Turkish patients diagnosed with schizophrenia based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), and 116 healthy control subjects participated in the present study. The genotype characteristics were determined by polymerase chain reaction-based restriction fragment length polymorphism method using DNA extracted from peripheral blood.
Significant differences in both the genotype and allele frequencies were found between schizophrenia patients and control groups (P < 0.01).
These findings may support the hypothesis that activation of the inflammatory response system and in particular, of Th-1 cells, is involved in the pathophysiology of schizophrenia. We think that this study is the first trial associated with IL-12 cytokine at the molecular genetic level on immune mechanisms for neuropsychiatric disorders including schizophrenia, and this perspective and the role of the cytokines in the pathogenesis of schizophrenia may constitute a reasonable target for the present and future treatment strategies and prognosis.
有假说认为，免疫系统的激活可能参与了精神分裂症患者中枢神经系统发生的神经病理变化。细胞因子在免疫系统激活中起关键作用。此外，它们对多巴胺能、去甲肾上腺素能和5-羟色胺能神经传递有强烈影响。据我们所知，在精神分裂症患者中，仅在一项研究中检测了白细胞介素（IL）-12的血浆水平，该研究确定了IL-12失调。然而，尚未对精神分裂症患者的IL-12B（p40）基因的基因型变异进行研究。因此，在本研究中，我们旨在检测土耳其东安纳托利亚省埃拉泽格地区人群中精神分裂症患者IL-12B（p40）基因启动子区域的多态性变异。
100例根据《精神障碍诊断与统计手册》（DSM-IV）诊断为精神分裂症的土耳其患者和116名健康对照者参与了本研究。使用从外周血提取的DNA，通过基于聚合酶链反应的限制性片段长度多态性方法确定基因型特征。
精神分裂症患者与对照组之间在基因型和等位基因频率上均存在显著差异（P < 0.01）。
这些发现可能支持以下假说，即炎症反应系统尤其是Th-1细胞的激活参与了精神分裂症的病理生理学过程。我们认为，本研究是在分子遗传学水平上首次针对包括精神分裂症在内的神经精神疾病免疫机制与IL-12细胞因子相关的试验，并且这种观点以及细胞因子在精神分裂症发病机制中的作用可能构成当前和未来治疗策略及预后的合理靶点。
