Kanazawa Tetsufumi, Glatt Stephen J, Tsutsumi Atsushi, Kikuyama Hiroki, Koh Jun, Yoneda Hiroshi, Tsuang Ming T
Department of Psychiatry, Center for Behavioral Genomics, University of California, San Diego, La Jolla, California 92093, USA.
Am J Med Genet B Neuropsychiatr Genet. 2007 Jan 5;144B(1):113-6. doi: 10.1002/ajmg.b.30367.
Increasing evidence has supported the hypothesis of a neurodevelopmental component in the etiology of schizophrenia. Recently, several independent microarray gene expression studies have revealed downregulated expression of myelin-related genes in the postmortem brains of schizophrenia patients. Complete myelination of the cortex has been observed to occur in late adolescence and early adulthood, which is typically the age of onset of schizophrenia. ERBB3 is a gene which has not only been found to be downregulated in schizophrenia simultaneously in three microarray studies, but also is a strong candidate because of its potential role in neurodevelopment as a receptor of NRG1. Therefore, we performed association analysis of seven nonsynonymous SNPs in this gene. Two SNPs in ERBB3 (rs773123 and rs2271188) were polymorphic in our samples, neither of which showed significant evidence of association with the illness (P = 0.639 and 0.561, respectively). Because replication across such studies is notoriously difficult, the microarray evidence implicating ERBB3 still strongly supports some role of this gene in schizophrenia. However, our failure to find genetic association suggests that the differential expression of ERBB3 in schizophrenia may be environmentally driven, or involve cis- or trans-acting genetic factors beyond the boundaries of the gene itself.
越来越多的证据支持精神分裂症病因中存在神经发育成分的假说。最近，几项独立的微阵列基因表达研究表明，精神分裂症患者死后大脑中髓鞘相关基因的表达下调。已观察到皮质的完全髓鞘化发生在青春期晚期和成年早期，而这通常是精神分裂症的发病年龄。ERBB3是一个基因，它不仅在三项微阵列研究中同时被发现在精神分裂症中表达下调，而且由于其作为NRG1受体在神经发育中的潜在作用，它也是一个强有力的候选基因。因此，我们对该基因中的七个非同义单核苷酸多态性（SNP）进行了关联分析。ERBB3中的两个SNP（rs773123和rs2271188）在我们的样本中具有多态性，但两者均未显示出与该疾病存在显著关联的证据（P值分别为0.639和0.561）。由于在这类研究中进行重复验证非常困难，微阵列研究中涉及ERBB3的证据仍然有力地支持了该基因在精神分裂症中发挥某种作用。然而，我们未能发现基因关联表明，ERBB3在精神分裂症中的差异表达可能是由环境驱动的，或者涉及该基因本身范围之外的顺式或反式作用遗传因素。
