NMDA受体NR1亚单位基因与精神分裂症的连锁分析

A linkage study of N-Methyl-D-Aspartater receptor NR1 subunit gene and schizophrenia.

目的了解N-甲基-D-天冬氨酸(NMDA)受体NR1亚单位基因与精神分裂症的连锁关系。方法选取NR1亚单位基因所在区域的2个微卫星标记D9s1838和D9s1826,对94个符合美国精神障碍诊断与统计手册第4版精神分裂症诊断标准(DSM-Ⅳ)的中国汉族精神分裂症受累同胞对及家系成员共376个个体作基因分型,其中男性194名,女性182名。采用美国国立精神卫生研究所(NIMH)制订的《遗传研究诊断问卷》(DIGS),对家系成员躯体和精神状况进行评定;采用NIMH制订的《遗传研究家族问卷》(FIGS)了解家系结构。选用GENEHUNTER2.1软件对分型资料进行非参数连锁分析。结果两点、多点非参数分析最大LOD值均位于D9s1826,分别为1.70(P=0.050),2.08(P=0.015),两者均大于验证性连锁阈值1.2。结论NR1基因区域微卫星标记与精神分裂症存在验证性连锁关系,提示NR1基因可能为精神分裂症的易感基因之一。

Objective To investigate the linkage relationship betweeen NR1 gene locus and schizophrenia. Methods Altogether 376 subjects from 94 families were recruited, including 94 affected sib-pairs and their relatives. The subjects were interviewed with Diagnostic Interview for Genetic Studies（DIGS） and Family Interview for Genetic Studies（FIGS）. All enrolled patients met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition （ DSM-IV ） diagnosis of schizophrenia. Two microsatellite polymorphisms of NR1 gene region were determined after the polymerase chain reaction. Nonparametric linkage analysis was performed with GENEHUNTER software version 2. 1. Results The maximum two-point nonparametric linkage analysis LOD scores of 1.70 （P = 0. 050） and multipoint nonparametric linkage analysis LOD scores of 2. 08 （P =0. 015） were obtained at marker D9s1826. Conclusion NR1 gene might contribute to the genetic etiology of schizophrenia in Chinese population, but further study is needed.