The interaction of BDNF and NTRK2 gene increases the susceptibility of paranoid schizophrenia.
The interaction of BDNF and NTRK2 gene increases the susceptibility of paranoid schizophrenia.
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BDNF 与 NTRK2 基因的相互作用增加偏执型精神分裂症的易感性
DOI：
10.1371/journal.pone.0074264
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Cui D
中科院分区：
文献类型：
--
作者：
Lin Z;Su Y;Zhang C;Xing M;Ding W;Liao L;Guan Y;Li Z;Cui D
BDNF基因功能Val66Met多态rs6265与精神分裂症的相关性尚不一致。除了精神分裂症本身的异质性导致结果不一致外，多基因之间的相互作用可能在精神分裂症的发病机制中起主要作用，而不是单基因。神经营养酪氨酸激酶受体2(NTRK2)是脑源性神经营养因子的高亲和力受体，与心境障碍有关，但尚无文献报道与精神分裂症有关。因此，本研究以402例偏执型精神分裂症患者为研究对象，以406例健康对照为研究对象，探讨了神经源性神经营养因子基因rs6265、NTRK2基因3个多态(rs1387923、rs2769605和rs1565445)在中国汉族人群偏执型精神分裂症易感性中的作用及其相互作用。我们没有观察到患者和健康对照组之间的等位基因和基因型频率在所有四个多态上的显著差异。单倍型分析也显示NTRK2基因的单倍型(rs1387923、rs2769605和rs1565445)与偏执型精神分裂症无关。然而，我们通过MDR方法和常规统计分析发现BDNF和NTRK2的相互作用与偏执型精神分裂症之间的关联。最佳的基因-基因互作模型是三位点模型(BDNFrs6265、NTRK2 rs1387923和NTRK2 rs2769605)，其中包括一个低危和三个高危四位点基因组合。提示BDNF和NTRK2基因rs6265、rs1387923、rs2769605和rs1565445的单一多态与汉族人偏执型精神分裂症的发病无关，但BDNF和NTRK2基因的交互作用(BDNF-rs6265、NTRK2-rs1387923和NTRK2-rs2769605)可能与偏执型精神分裂症的易感性有关。
The association between BDNF gene functional Val66Met polymorphism rs6265 and the schizophrenia is far from being consistent. In addition to the heterogeneous in schizophrenia per se leading to the inconsistent results, the interaction among multi-genes is probably playing the main role in the pathogenesis of schizophrenia, but not a single gene. Neurotrophic tyrosine kinase receptor 2 (NTRK2) is the high-affinity receptor of BDNF, and was reported to be associated with mood disorders, though no literature reported the association with schizophrenia. Thus, in the present study, total 402 patients with paranoid schizophrenia (the most common subtype of schizophrenia) and matched 406 healthy controls were recruited to investigate the role of rs6265 in BDNF, three polymorphisms in NTRK2 gene (rs1387923, rs2769605 and rs1565445) and their interaction in the susceptibility to paranoid schizophrenia in a Chinese Han population. We did not observe significant differences in allele and genotype frequencies between patients and healthy controls for all four polymorphisms separately. The haplotype analysis also showed no association between haplotype of NTRK2 genes (rs1387923, rs2769605, and rs1565445) and paranoid schizophrenia. However, we found the association between the interaction of BDNF and NTRK2 with paranoid schizophrenia by using the MDR method followed by conventional statistical analysis. The best gene-gene interaction model was a three-locus model (BDNF rs6265, NTRK2 rs1387923 and NTRK2 rs2769605), in which one low-risk and three high-risk four-locus genotype combinations were identified. Our findings implied that single polymorphism of rs6265 rs1387923, rs2769605, and rs1565445 in BDNF and NTRK2 were not associated with the development of paranoid schizophrenia in a Han population, however, the interaction of BDNF and NTRK2 genes polymorphisms (BDNF-rs6265, NTRK2-rs1387923 and NTRK2-rs2769605) may be involved in the susceptibility to paranoid schizophrenia.
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影响因子：
2.6
作者：
Dervieux, Thierry;Wessels, Judith A. M.;Guchelaar, Henk-Jan
通讯作者：
Guchelaar, Henk-Jan
影响因子：
5.3
作者：
Pezawas, L;Verchinski, BA;Weinberger, DR
通讯作者：
Weinberger, DR
影响因子：
9.8
作者：
Ritchie, MD;Hahn, LW;Moore, JH
通讯作者：
Moore, JH
影响因子：
6.1
作者：
Issa, George;Wilson, Christina;Pillai, Anilkumar
通讯作者：
Pillai, Anilkumar
影响因子：
5.3
作者：
Hashimoto, T;Bergen, SE;Lewis, DA
通讯作者：
Lewis, DA