TNF-α-1031 T/C基因多态性与精神分裂症患者发病年龄、认知功能的关系

TNF-α-1031 T/C polymorphisms is associated with cognitive dysfunction in chronic schizophrenia

目的研究TNF-α-1031 T/C基因多态性与精神分裂症患者发病年龄、认知功能的关系。方法选择486例住院精神分裂症患者为观察组,319例年龄、性别、受教育年限与观察组相匹配健康志愿者为对照组,采用重复性成套神经心理状态测验(RBANS)评估其认知功能,采用聚合酶链式反应-限制性酶切片段长度多态性(PCR-RFLP)法进行基因分型,分析TNF-α-1031T/C基因多态性与精神分裂症患者发病年龄、认知功能的关系。结果观察组与对照组TNF-α-1031 T/C基因型及等位基因分布频率比较,差异均无统计学意义(均P>0.05)。TT基因型与TC+CC基因型的精神分裂症患者年龄,性别,病程,阳性与阴性症状量表(PANSS)总分及各因子得分,RBANS的注意、言语功能及延迟记忆等分量表得分比较,差异均无统计学意义(均P>0.05)。TT基因型患者发病年龄小于TC+CC基因型患者,RBANS总分及即刻记忆、视觉广度等分量表得分均低于TC+CC基因型,差异均有统计学意义(均P<0.05)。精神分裂症患者发病年龄与RBANS总分及注意、即刻记忆、延迟记忆等分量表得分均呈正相关(r=0.179、0.102、0.154和0.134,均P<0.05),与视觉广度、言语功能分量表得分均未见相关(r=0.149和0.138,均P>0.05)。中介效应模型分析发现,精神分裂症患者发病年龄在认知功能损害中发挥了部分中介的作用(R2=0.13,P<0.01)。结论 TNF-α-1031 T/C基因多态性可能是引起精神分裂症患者认知功能损害的原因之一,或通过影响发病年龄而导致认知功能损害。

Objective To investigate the association of TNF-α-1031 T/C polymorphisms with the age of onset and cognitive functions of patients with schizophrenis. Methods Total 486 patients with schizophrenia and 310 age-, sex-and education level-matched healthy subjects(control group) were enrolled in the study. Cognitive functions were measured by RBANS and symptoms were assessed by PANSS. The TNF-α-1031 T/C polymorphisms were detected by PCR-RFLP. Results There were no significant differences in allelic frequency and genotype frequency in TNF-α-1031 T/C between patients and normal controls. However, the TNF-α-1031 T/C polymorphisms were significantly associated with the age of onset(P<0.05),immediate memory, visuospatial, total score of RBANS(P<0.05) in schizophranic patients. The age of onset was related to attention, immediate memory, delayed memory and total score of RBANS(r=0.179, 0.102, 0.154, 0.134, all P<0.05). It is significant for the mediation analysis for the relationship across TNF-α-1031 T/C polymorphism, age of onset and cognitive functions. Conclusion The results indicate that TNF-α-1031 T/C polymorphism may be one of the causes for cognitive impairments, which may be associated with the age of onset in patients with schizophrenia.