Xenobiotic metabolizing and transporter genes: gene-gene interactions in schizophrenia and related disorders
Xenobiotic metabolizing and transporter genes: gene-gene interactions in schizophrenia and related disorders
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DOI：
10.2217/pgs.10.158
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发表时间：
2010-12-01
期刊：
影响因子：
2.1
通讯作者：
Lafuente, Amalia
中科院分区：
文献类型：
--
作者：
Gasso, Patricia;Mas, Sergi;Lafuente, Amalia
目的：在本研究中，我们探讨了精神分裂症及相关疾病中 CYP2D6（*3、*4、*5、*6 和 *1xN）、CYP3A5（*3）、CYP1A2（*1C 和 *1F）和 ABCB1（G2677T）之间可能存在的上位性。材料与方法：共有 344 名被诊断患有精神分裂症及相关疾病的患者和 484 名健康对照者参与了本研究。我们通过多因素降维分析了基因基因相互作用。结果：包含 ABCB1 G2677T、CYP3A5*3、CYP1A2*1F 和 CYP2D6*4 变体的四向模型具有最佳的整体性能（准确度：0.573），交叉验证一致性为 10/10（排列测试 p < 0.004）。结论：我们的结果表明 CYP 和转运蛋白在脑代谢和稳态中具有重要作用，并提供了精神分裂症背景下异生物质代谢和转运蛋白基因之间基因相互作用的证据。
Aims: In this study we explored possible epistasis between CYP2D6 (*3, *4, *5, *6 and *1xN), CYP3A5 (*3), CYP1A2 (*1C and *1F) and ABCB1 (G2677T) in schizophrenia and related disorders. Materials & methods: A total of 344 patients diagnosed with schizophrenia and related disorders, and 484 healthy controls participated in the present study. We analyzed gene gene interactions by multifactor dimensionality reduction. Results: A four-way model including ABCB1 G2677T, CYP3A5*3, CYP1A2*1F and CYP2D6*4 variants had the best overall performances (accuracy: 0.573) and a crossvalidation consistency of 10/10 (permutation testing p < 0.004). Conclusion: Our results suggest a significant involvement of CYPs and transporters in brain metabolism and homeostasis, and provide evidence of gene gene interactions among xenobiotic metabolizing and transporter genes in the context of schizophrenia.