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对患有精神分裂症、分裂情感性障碍和双相情感障碍的墨西哥患者的ZNF804A基因进行遗传分析。

Genetic analysis of the ZNF804A gene in Mexican patients with schizophrenia, schizoaffective disorder and bipolar disorder.

作者信息

Münch-Anguiano Lucía, Camarena Beatriz, Nieto-Quinto Jesica, de la Torre Patricia, Pedro Laclette Juan, Hirata-Hernández Harumi, Hernández-Muñoz Sandra, Aguilar-García Alejandro, Becerra-Palars Claudia, Gutiérrez-Mora Doris, Ortega-Ortiz Hiram, Escamilla-Orozco Raúl, Saracco-Álvarez Ricardo, Bustos-Jaimes Ismael

机构信息

Dirección de Servicios Clínicos, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Ciudad de México, Mexico; Programa de Maestría y Doctorado en Ciencias Médicas y Odontológicas de la Salud, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.

Departamento de Farmacogenética, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Ciudad de México, Mexico.

出版信息

Gene. 2022 Jun 30;829:146508. doi: 10.1016/j.gene.2022.146508. Epub 2022 Apr 18.

Abstract

BACKGROUND

Evidence suggests that schizophrenia (SCZ), schizoaffective disorder (SAD) and bipolar disorder (BPD) share genetic risk variants. ZNF804A gene has been associated with these disorders in different populations. GWAS and candidate gene studies have reported association between the rs1344706 A allele with SCZ, SAD and BPD in European and Asian populations. In Mexican patients, no studies have specifically analyzed ZNF804A gene variants with these disorders. The aim of the study was to analyze the rs1344706 and identify common and rare variants in a targeted region of the ZNF804A gene in Mexican patients with SCZ, BPD and SAD compared with a control group.

METHODS

We genotyped the rs1344706 in 228 Mexican patients diagnosed with SCZ, SAD and BPD, and 295 controls. Also, an additional sample of 167 patients with these disorders and 170 controls was analyzed to identify rare and common variants using the Sanger-sequence analysis of a targeted region of ZNF804A gene.

RESULTS

Association analysis of rs1344706 observed a higher frequency of A allele in the patients compared with the control group; however, did not show statistical differences after Bonferronís correction (χ2 = 5.3, p = 0.0208). In the sequence analysis, we did not identify rare variants; however, we identified three common variants: rs3046266, rs1366842 and rs12477430. A comparison of the three identified variants between patients and controls did not show statistical differences (p > 0.0125). Finally, haplotype analysis did not show statistical differences between SCZ, SAD and BPD and controls.

CONCLUSIONS

Our findings did not support the evidence suggesting that ZNF804A gene participates in the etiology of SCZ, SAD and BPD. Future studies are needed in a larger sample size to identify the effect of this gene in psychiatric disorders.

摘要

背景

有证据表明,精神分裂症(SCZ)、分裂情感性障碍(SAD)和双相情感障碍(BPD)存在共同的遗传风险变异。ZNF804A基因在不同人群中均与这些疾病相关。全基因组关联研究(GWAS)和候选基因研究报告称,在欧洲和亚洲人群中,rs1344706 A等位基因与SCZ、SAD和BPD存在关联。在墨西哥患者中,尚无研究专门分析ZNF804A基因变异与这些疾病的关系。本研究的目的是分析rs1344706,并确定墨西哥SCZ、BPD和SAD患者与对照组相比,ZNF804A基因靶向区域中的常见和罕见变异。

方法

我们对228例诊断为SCZ、SAD和BPD的墨西哥患者以及295例对照进行了rs1344706基因分型。此外,还对另外167例患有这些疾病的患者和170例对照进行了样本分析,通过对ZNF804A基因靶向区域进行桑格测序分析来确定罕见和常见变异。

结果

rs1344706的关联分析显示,与对照组相比,患者中A等位基因的频率更高;然而,经Bonferroni校正后未显示出统计学差异(χ2 = 5.3,p = 0.0208)。在序列分析中,我们未发现罕见变异;但是,我们鉴定出了三个常见变异:rs3046266、rs1366842和rs12477430。患者与对照之间这三个已鉴定变异的比较未显示出统计学差异(p > 0.0125)。最后,单倍型分析在SCZ、SAD和BPD与对照之间未显示出统计学差异。

结论

我们的研究结果不支持ZNF804A基因参与SCZ、SAD和BPD病因学的证据。未来需要更大样本量的研究来确定该基因在精神疾病中的作用。

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