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使用高分辨率熔解曲线分析技术对精神分裂症和双相情感障碍精神病患者的CYP1A2、CYP2C9、CYP2C19和CYP2D6基因多态性进行表征以实现个性化医疗。

Characterization CYP1A2, CYP2C9, CYP2C19 and CYP2D6 Polymorphisms Using HRMA in Psychiatry Patients with Schizophrenia and Bipolar Disease for Personalized Medicine.

作者信息

Yenilmez Ebru Dundar, Tamam Lut, Karaytug Onur, Tuli Abdullah

机构信息

Medical Biochemistry, Faculty of Medicine, University of Cukurova, Adana, Turkey.

Psychiatry, Faculty of Medicine, University of Cukurova, Adana, Turkey.

出版信息

Comb Chem High Throughput Screen. 2018;21(5):374-380. doi: 10.2174/1386207321666180619164726.

DOI:10.2174/1386207321666180619164726
PMID:29921201
Abstract

BACKGROUND

The interindividual genetic variations in drug metabolizing enzymes effects the impact and toxicity in plenty of drugs.

OBJECTIVE

CYP1A2, CYP2C9, CYP2C19 and CYP2D6 gene polymorphisms were characterized using high resolution melting analysis (HRMA) in follow-up patients in psychiatry clinic as a preliminary preparation for personalized medicine.

METHOD

Genotyping of CYP1A2*1F, CYP2C9 *2, *3, CYP2C19 *2, *3 and *17 and CYP2D6 *3, *4 was conducted in 101 patients using HRMA. Genotype and allele frequencies of the CYP variants were found to be in equilibrium with the Hardy-Weinberg equation.

RESULTS

The frequency of the CYP1A21F allele in schizophrenia and bipolar disease was 0.694 and 0.255, respectively. The CYP2C9 allele frequencies were 0.087 (CYP2C92), and 0.549 (CYP2C93) for bipolar; 0.278 (CYP2C92) and 0.648 (CYP2C93) in schizophrenias. The CYP2C192 and *17 allele frequencies was 0.111 and 0.185 in schizophrenia and variant 2 was 0.117 and variant 17 was 0.255 in bipolar group. The frequency of the CYP2D63 allele was 0.027 in schizophrenias. The frequencies for the CYP2D64 variant were 0.092 and 0.096 in schizophrenia and bipolar groups, respectively.

CONCLUSION

The knowledge in pharmacogenomic and also the developments in molecular genetics are growing rapidly. In future, this can be expected to provide new methodologies in the prediction of the activity in drug metabolizing enzymes. The HRMA is a rapid and useful technique to identify the genotypes for drug dosage adjustment before therapy in psychiatry patients.

摘要

背景

药物代谢酶的个体间基因变异会影响多种药物的作用和毒性。

目的

采用高分辨率熔解分析(HRMA)对精神科门诊随访患者的CYP1A2、CYP2C9、CYP2C19和CYP2D6基因多态性进行分析,为个性化医疗做初步准备。

方法

采用HRMA对101例患者进行CYP1A2*1F、CYP2C9 *2、*3、CYP2C19 *2、3和17以及CYP2D6 *3、*4基因分型。发现CYP变异体的基因型和等位基因频率符合Hardy-Weinberg平衡。

结果

精神分裂症和双相情感障碍患者中CYP1A21F等位基因频率分别为0.694和0.255。双相情感障碍患者中CYP2C9等位基因频率分别为0.087(CYP2C92)和0.549(CYP2C93);精神分裂症患者中分别为0.278(CYP2C92)和0.648(CYP2C93)。精神分裂症患者中CYP2C192和17等位基因频率分别为0.111和0.185,双相情感障碍组中变异体2为0.117,变异体17为0.255。精神分裂症患者中CYP2D63等位基因频率为0.027。精神分裂症和双相情感障碍组中CYP2D6*4变异体频率分别为0.092和0.096。

结论

药物基因组学知识和分子遗传学发展迅速。未来,有望为预测药物代谢酶活性提供新方法。HRMA是一种快速且有用的技术,可用于在精神科患者治疗前识别基因型以调整药物剂量。

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