NMDA 受体亚单位和多巴胺受体基因变异与氯氮平反应的基因-基因相互作用分析。
Gene-gene interaction analyses between NMDA receptor subunit and dopamine receptor gene variants and clozapine response.
机构信息
Neurogenetics Section, Centre for Addiction & Mental Health, 250 College Street, Toronto, Ontario, 5T1R8, Canada.
出版信息
Pharmacogenomics. 2011 Feb;12(2):277-91. doi: 10.2217/pgs.10.182.
AIMS
To investigate the possible association and gene-gene interaction effects of polymorphisms in NMDA receptor subunit (GRIN1, GRIN2A and GRIN2B) and dopamine receptor (DRD1, DRD2 and DRD3) genes with clozapine response.
MATERIALS & METHODS: GRIN1 rs11146020 (G1001C), GRIN2A GT-repeat and GRIN2B rs10193895 (G-200T) polymorphisms were tested for association in a Caucasian (n = 183) and an African-American (n = 49) sample using χ(2) and ANOVA tests. Logistic regression and two-way ANOVA were used to explore gene-gene interaction effects with dopamine receptor gene variants.
RESULTS & CONCLUSION: This study does not support the involvement of the NMDA receptor subunit gene polymorphisms in clozapine response. All tests for an association were negative. Gene-gene interaction analyses however yielded promising leads, including an observed effect between DRD1 rs686 and DRD3 Ser9Gly polymorphisms on clozapine response (p = 0.002).
目的
研究 NMDA 受体亚基（GRIN1、GRIN2A 和 GRIN2B）和多巴胺受体（DRD1、DRD2 和 DRD3）基因多态性与氯氮平反应之间可能存在的关联和基因-基因相互作用效应。
材料与方法
使用 χ(2)检验和方差分析检验了高加索人（n=183）和非裔美国人（n=49）样本中 NMDA 受体亚基基因 GRIN1 rs11146020（G1001C）、GRIN2A GT 重复和 GRIN2B rs10193895（G-200T）多态性与氯氮平反应之间的关联。采用 logistic 回归和双向方差分析探索与多巴胺受体基因变异的基因-基因相互作用效应。
结果与结论
本研究不支持 NMDA 受体亚基基因多态性与氯氮平反应有关。所有关联检验均为阴性。然而，基因-基因相互作用分析提供了一些有希望的线索，包括 DRD1 rs686 和 DRD3 Ser9Gly 多态性对氯氮平反应的观察到的效应（p=0.002）。
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