Association Study of KCNH7 Polymorphisms and Individual Responses to Risperidone Treatment in Schizophrenia
Association Study of KCNH7 Polymorphisms and Individual Responses to Risperidone Treatment in Schizophrenia
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KCNH7 多态性与精神分裂症利培酮治疗个体反应的关联研究
DOI：
10.3389/fpsyt.2019.00633
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发表时间：
2019-08
影响因子：
4.7
通讯作者：
Yue W
中科院分区：
文献类型：
--
作者：
Wang X;Su Y;Yan H;Huang Z;Huang Y;Yue W
利培酮已被用于治疗精神分裂症的症状并减少其复发。然而，对治疗的反应在患者之间显示出很大的差异。钾通道已被报道为抗精神病药物的有效靶点。KCNH 7是电压门控K+通道Kv 11家族的成员，主要在脑中表达。在这里，我们评估了393例精神分裂症患者中KCNH 7与利培酮反应的遗传相关性。两组均给予利培酮治疗6周。测定阳性和阴性症状量表（PANSS）评分的减少率，以量化药物反应。我们还研究了KCNH 7的6个单核苷酸多态性（SNPs）与利培酮反应之间的关联，共6周。KCNH 7基因内含子中的SNP rs77699177（C > T）与PANSS减分率反映的治疗反应显著相关（CC，55.8 ± 23.0; TC，70.9 ± 20.3，P = 0.000110），表明TC基因型患者抗精神病药物治疗的疗效更好。rs 2241240 SNP也显示出与治疗6周后的治疗反应显著相关（P = 0.00256）。研究结果表明，电压门控性K+通道KCNH 7是一个潜在的功能标志物，用于识别精神分裂症患者对利培酮治疗的反应。注：本研究注册于临床试验编号ChiCTR-RNC-09000522（http：//www.chictr.org/）。
Risperidone has been used to treat the symptoms of schizophrenia and to reduce its relapse. However, the responses to treatment show great variability among patients. The potassium channel has been reported as an effective target for antipsychotics. KCNH7, a member of the voltage-gated K+ channel Kv11 family, is primarily expressed in the brain. Here, we assessed the genetic association of KCNH7 with risperidone responses in 393 schizophrenia patients. The patients were treated with risperidone for 6 weeks. The reduction rates of Positive and Negative Syndrome Scale (PANSS) scores were determined to quantify drug response. We also examined the associations between six single-nucleotide polymorphisms (SNPs) of KCNH7 and the risperidone responses for a total of 6 weeks. The SNP rs77699177 (C > T) in the KCNH7 gene intron was significantly associated with the treatment response reflected by the PANSS reduction rate (CC, 55.8 ± 23.0; TC, 70.9 ± 20.3, P = 0.000110), indicating that patients with the TC genotype have better efficacy for antipsychotic therapy. The rs2241240 SNP also showed a significant association with treatment responses after 6 weeks of treatment (P = 0.00256). The findings indicate that the voltage-gated K+ channel KCNH7 is a potential functional marker for the identification of the response to risperidone treatment in schizophrenia patients. Note: The study was registered under clinical trial number ChiCTR-RNC-09000522 (http://www.chictr.org/).
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影响因子：
4.3
作者：
Zhang JP;Malhotra AK
通讯作者：
Malhotra AK
影响因子：
3.5
作者：
Strauss KA;Markx S;Georgi B;Paul SM;Jinks RN;Hoshi T;McDonald A;First MB;Liu W;Benkert AR;Heaps AD;Tian Y;Chakravarti A;Bucan M;Puffenberger EG
通讯作者：
Puffenberger EG
影响因子：
6.2
作者：
Griswold AJ;Dueker ND;Van Booven D;Rantus JA;Jaworski JM;Slifer SH;Schmidt MA;Hulme W;Konidari I;Whitehead PL;Cuccaro ML;Martin ER;Haines JL;Gilbert JR;Hussman JP;Pericak-Vance MA
通讯作者：
Pericak-Vance MA
DOI：
10.1038/sj.tpj.6500211
发表时间：
2003-12
期刊：
The Pharmacogenomics Journal
影响因子：
--
作者：
Y. Yamanouchi;N. Iwata;Tatsuyo Suzuki;T. Kitajima;M. Ikeda;N. Ozaki
通讯作者：
Y. Yamanouchi;N. Iwata;Tatsuyo Suzuki;T. Kitajima;M. Ikeda;N. Ozaki
DOI：
10.4135/9781412963947.n57
发表时间：
2020-02
期刊：
Definitions
影响因子：
--
作者：
P. Woratanarat
通讯作者：
P. Woratanarat