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一项关于双相情感障碍患者的多态性与治疗反应之间的关联的纵向研究。

A Longitudinal Study of the Association between the Polymorphism and Treatment Response in Patients with Bipolar Disorder.

机构信息

Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.

School of Pharmacy, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.

出版信息

Int J Mol Sci. 2022 Aug 25;23(17):9635. doi: 10.3390/ijms23179635.

Abstract

Patients with bipolar disorder (BD) exhibit individual variability in the treatment outcome, and genetic background could contribute to BD itself and the treatment outcome. Leptin levels significantly change in BD patients treated with valproate (VPA), but whether polymorphisms are associated with treatment response is still unknown. This longitudinal study aimed to investigate the associations between polymorphisms and VPA treatment response in BD patients who were drug naïve at their first diagnosis of BD. The single-nucleotide polymorphisms (SNPs) of (rs1137101, rs1137100, rs8179183, and rs12145690) were assayed, and the polymorphism frequencies of alleles and genotypes were not significantly different between the controls ( = 77) and BD patients ( = 130). In addition, after the 12-week course of VPA treatment in BD patients, the polymorphisms showed significant effects on changes in disease severity. Moreover, considering the effect of the haplotype, the frequency of the CAGG haplotype in BD patients was higher than that in the controls (9.3 vs. 2.9%, = 0.016), and the CAGG haplotype was associated with a better treatment response than the other haplotypes in BD patients receiving VPA treatment. Therefore, polymorphisms might serve as mediators involved in the therapeutic action of VPA treatment.

摘要

双相障碍 (BD) 患者的治疗结果存在个体差异,遗传背景可能导致 BD 本身和治疗结果的差异。接受丙戊酸钠 (VPA) 治疗的 BD 患者的瘦素水平会显著变化,但多态性是否与治疗反应相关仍不清楚。这项纵向研究旨在探讨初诊为 BD 的药物初治患者中 多态性与 VPA 治疗反应之间的关联。检测了单核苷酸多态性 (SNPs) (rs1137101、rs1137100、rs8179183 和 rs12145690),等位基因和基因型的 多态性频率在对照组(=77)和 BD 患者组(=130)之间没有显著差异。此外,在 BD 患者接受 VPA 治疗 12 周后, 多态性对疾病严重程度的变化有显著影响。此外,考虑到 单倍型的影响,BD 患者中 CAGG 单倍型的频率高于对照组(9.3%比 2.9%,=0.016),并且与其他单倍型相比,BD 患者接受 VPA 治疗时,CAGG 单倍型与更好的治疗反应相关。因此, 多态性可能作为参与 VPA 治疗治疗作用的介质。

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