A preliminary genetic association study of GAD1 and GABAB receptor genes in patients with treatment-resistant schizophrenia
A preliminary genetic association study of GAD1 and GABAB receptor genes in patients with treatment-resistant schizophrenia
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DOI：
10.1007/s11033-021-07019-z
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发表时间：
2021-11-29
影响因子：
2.8
通讯作者：
Iyo，Masaomi
中科院分区：
文献类型：
--
作者：
Miyazawa，Atsuhiro;Kanahara，Nobuhisa;Iyo，Masaomi
背景GABA能系统功能障碍与精神分裂症的病因学有关，尤其是与认知功能障碍有关。难治性精神分裂症（TRS）患者除了严重的阳性症状外，普遍存在严重的认知功能障碍，这表明GABA系统功能障碍可能与TRS患者有更密切的关系。方法和结果本研究对14例TRS患者进行了外显子组测序，在GAD 1、GABBR 1和GABBR 2基因上发现了4个SNP。然后在357例TRS患者、682例非TRS患者和508例健康对照（HC）中进行包括这4个SNP和rs3749034 onGAD 1as的5个SNP的关联研究。结果显示，任何五个SNP的等位基因和/或遗传分布没有显着差异。然而，精神分裂症和HC组之间以及三组之间的比较的几个亚组分析显示，rs3749034对GAD 1和rs 10985765/rs3750344对GABBR 2具有名义水平的显著性。特别是，在女性受试者的比较中，对rs3749034的严格分析显示，精神分裂症和HC组之间以及TRS和HC groups.ConclusionsSeveral阳性结果表明，GABA系统对精神分裂症或TRS的遗传易感性可能受到性别或采样区域的影响，总体而言，GAD 1上的rs3749034和GABBR 2上的rs 10985765可能与TRS有关。在本研究中，仅检查了少数SNPs;在本初步研究中可能未捕获GABA相关基因的其他区域中的其他重要遗传变异。
BackgroundGABAergic system dysfunction has been implicated in the etiology of schizophrenia and of cognitive impairments in particular. Patients with treatment-resistant schizophrenia (TRS) generally suffer from profound cognitive impairments in addition to severe positive symptoms, suggesting that GABA system dysfunction could be involved more closely in patients with TRS.Methods and resultsIn the present study, exome sequencing was conducted on fourteen TRS patients, whereby four SNPs were identified onGAD1,GABBR1andGABBR2genes. An association study for five SNPs including these 4 SNPs and rs3749034 onGAD1as then performed among 357 patients with TRS, 682 non-TRS patients and 508 healthy controls (HC). The results revealed no significant differences in allelic and/or genetic distributions for any of the five SNPs. However, several subanalyses in comparisons between schizophrenia and HC groups, as well as between the three groups, showed nominal-level significance for rs3749034 onGAD1and rs10985765/rs3750344 onGABBR2. In particular, in comparisons of female subjects, rigorous analysis for rs3749034 showed a statistical difference between the schizophrenia and HC groups and between the TRS and HC groups.ConclusionsSeveral positive results in subanalyses suggested that genetic vulnerability in the GABA system to schizophrenia or TRS could be affected by sex or sampling area, and overall, that rs3749034 onGAD1and rs10985765 onGABBR2could be related to TRS. In the present study, only a few SNPs were examined; it is possible that other important genetic variants in other regions of GABA-related genes were not captured in this preliminary study.