Shiota Sae, Tochigi Mamoru, Shimada Hiroko, Ohashi Jun, Kasai Kiyoto, Kato Nobumasa, Tokunaga Katsushi, Sasaki Tsukasa
Department of Human Genetics, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655, Japan.
Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655, Japan.
J Hum Genet. 2008;53(10):929-935. doi: 10.1007/s10038-008-0332-9. Epub 2008 Aug 14.
Neuregulin 1 (NRG1) is one of the most promising candidate genes for schizophrenia. A number of replication studies have been conducted, although the results were inconsistent and no susceptible variant has yet been identified. The inconsistency might be attributed to the ethnic difference in allele and haplotype frequencies. However, it is equally possible that one or more genes interacting with NRG1 may also be implicated in schizophrenia and attribute to the inconsistency. To test the hypothesis, we conducted an interaction analysis between NRG1 and one of its receptor's (ERBB4) polymorphisms as well as the association analysis of the two genes associated with schizophrenia in Japanese. We observed no significant difference between patients and controls in allele frequencies or genotypic distributions of the 18 polymorphisms of the genes. The permutation test showed no significant differences in estimated haplotype frequencies between patients and controls, including the haplotype HAP(ICE). In the interaction analysis, significant interaction was observed between rs2919381 in NRG1 and rs7560730 in ERBB4 (P = 0.047, corrected). Thus, our results suggest the possibility that interaction between variants in NRG1 and ERBB4 might contribute to susceptibility for schizophrenia in a Japanese population. Further investigation may be necessary to confirm our results.
神经调节蛋白1（NRG1）是精神分裂症最有前景的候选基因之一。已经进行了多项重复研究，尽管结果不一致，且尚未鉴定出易感变异体。这种不一致可能归因于等位基因和单倍型频率的种族差异。然而，同样有可能的是，一个或多个与NRG1相互作用的基因也可能与精神分裂症有关，并导致了这种不一致。为了验证这一假设，我们对NRG1与其受体之一（ERBB4）的多态性进行了相互作用分析，并对日本人群中与精神分裂症相关的这两个基因进行了关联分析。我们观察到，患者和对照组在这些基因的18种多态性的等位基因频率或基因型分布上没有显著差异。排列检验显示，患者和对照组之间估计的单倍型频率没有显著差异，包括单倍型HAP(ICE)。在相互作用分析中，观察到NRG1中的rs2919381与ERBB4中的rs7560730之间存在显著相互作用（P = 0.047，校正后）。因此，我们的结果表明，NRG1和ERBB4变异体之间的相互作用可能导致日本人群对精神分裂症的易感性。可能需要进一步研究来证实我们的结果。
