精神分裂症中多巴胺和血清素遗传变异的关联。

Association of Genetic Variants of Dopamine and Serotonin In Schizophrenia.

机构信息

Institute of Molecular Biology NAS RA, Yerevan, Armenia; Russian-Armenian, University, Yerevan, Armenia.

Andranik Chavushyan, Institute of Molecular Biology NAS RA, Yerevan, Armenia.

出版信息

Arch Med Res. 2020 Jan;51(1):13-20. doi: 10.1016/j.arcmed.2019.12.011. Epub 2020 Feb 18.

DOI:10.1016/j.arcmed.2019.12.011

PMID:32086104

Abstract

BACKGROUND

Several studies indicated that antipsychotic treatment response and side effect manifestation can be different due to inter-individual variability in genetic variations.

AIM OF THE STUDY

Here we perform a case-control study to explore a potential association between schizophrenia and variants within the antipsychotic drug molecular targets (DRD1, DRD2, DRD3, HTR2A, HTR6) and metabolizing enzymes (CYP2D6, COMT) genes in Armenian population including also analysis of their possible relationship with disease clinical symptoms.

METHODS

A total of 18 SNPs was studied in patients with schizophrenia (n = 78) and healthy control subjects (n = 77) using MassARRAY genotyping.

RESULTS

We found that two studied genetic variants, namely DRD2 rs4436578C and HTR2A rs6314A are underrepresented in the group of patients compared to healthy subjects. After the correction for multiple testing, the rs4436578C variant remained significant while the rs6314A reported borderline significance. No significant differences in minor allele frequencies for other studied variants were identified. Also, a relationship between the genotypes and age of onset as well as disease duration has been detected.

CONCLUSIONS

The DRD2 rs4436578*C genetic variant might have protective role against schizophrenia, at least in Armenians.

摘要

背景

多项研究表明，由于个体遗传变异的不同，抗精神病药物的治疗反应和副作用表现可能存在差异。

目的

本研究旨在通过病例对照研究，探讨精神分裂症与抗精神病药物分子靶点（DRD1、DRD2、DRD3、HTR2A、HTR6）和代谢酶（CYP2D6、COMT）基因内变异之间的潜在关联，并分析其与疾病临床症状的可能关系。

方法

采用 MassARRAY 基因分型技术，对 78 例精神分裂症患者和 77 例健康对照者的 18 个 SNP 进行研究。

结果

与健康对照组相比，我们发现两个研究的遗传变异，即 DRD2 rs4436578C 和 HTR2A rs6314A，在患者组中表达不足。经过多重检验校正后，rs4436578C 变异仍具有显著性，而 rs6314A 则具有边缘显著性。其他研究变异的次要等位基因频率无显著差异。此外，还检测到基因型与发病年龄和疾病持续时间之间的关系。