■下丘脑-垂体-肾上腺轴基因变异和儿童创伤(CT)被认为是自杀未遂(SA)的危险因素。本研究的目的是分析NR3C1,NR3C2和CT的基因x环境(GxE)相互作用,而NR3C1和NR3C2基因在SA发展中的表达与CT有关。
■共有516名墨西哥精神病患者来自美国国立心理研究所。其中,274具有SA至少一次,并且242没有SA。对所有患者的NR3C1和NR3C2遗传变异进行基因分型,从病历中获取CT信息。此外,NR3C1和NR3C2的基因表达也分析了96例患者的子样本,从儿童创伤问卷(CTQ)中获取TC信息。
■分析显示NR3C1,NR3C2和CT的GxE相互作用(OR=2.8,95%CI[1.9-3.9],p<0.0001)。在忽略的情况下也观察到了相互作用(OR=2.1,95%CI[1.4-3.1],p<0.0001),情感虐待(OR=2.1,95%CI[1.5-3],p<0.0001),和性虐待(OR=2.4,95%CI[1.4-2.9],p<0.0001)在SA的预测中。基因表达分析发现,在身体和性虐待得分较高(分别为p<0.0001;p<0.0006)和情感忽视(p=0.014)的SA患者中NR3C1过表达。观察到NR3C2的表达不足,除身体忽视外,与创伤亚型的得分高(p<0.0001)有关。此外,我们观察到NR3C1基因在具有rs6191的A等位基因的SA携带者中过度表达(p=0.0015)。此外,rs6198G等位基因携带者NR3C1基因过表达,rs5522G等位基因携带者NR3C2基因过表达(p<0.0001)。
■我们的研究结果表明,NR3C1和NR3C2的遗传变异差异影响表达水平,有CT病史的精神病患者对SA的易感性增加。
UNASSIGNED: Hypothalamic-pituitary-adrenal axis gene variants and childhood trauma (CT) are considered risk factors for suicide attempt (SA). The aim of the present study was analyzed gene x environment (GxE) interaction of NR3C1,
NR3C2, and CT, and NR3C1 and
NR3C2 gene expression in the development of SA with CT.
UNASSIGNED: A total of 516 psychiatric Mexican patients from Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz. Among them, 274 had SA at least once and 242 had not SA. Genetic variants of NR3C1 and
NR3C2 were genotyped in all the patients, of which were obtained the CT information from medical records. Additionally, the gene expression of NR3C1 and
NR3C2 was also analyzed for a subsample of 96 patients, obtaining the TC information from Childhood Trauma Questionnaire (CTQ).
UNASSIGNED: The analysis showed a GxE interaction of NR3C1,
NR3C2, and CT (OR=2.8, 95% CI [1.9-3.9], p<0.0001). Interactions were also observed with neglect (OR=2.1, 95% CI [1.4-3.1], p<0.0001), emotional abuse (OR=2.1, 95% CI [1.5-3], p<0.0001), and sexual abuse (OR=2.4, 95% CI [1.4-2.9], p<0.0001) in the prediction of SA. The analysis of gene expression identified an overexpression of NR3C1 in SA patients with high scores for physical and sexual abuse (p<0.0001; p<0.0006, respectively) and emotional neglect (p=0.014). An underexpression was observed of NR3C2, associated with high scores of trauma subtypes (p<0.0001) except physical neglect. Additionally, we observed an overexpression of NR3C1 gene in patients with SA carriers of A allele of rs6191 (p=0.0015). Also, overexpression of NR3C1 gene in carriers of G allele of rs6198 and underexpression of NR3C2 gene in carriers of G allele of rs5522 (p<0.0001).
UNASSIGNED: Our findings suggest that genetic variants of NR3C1 and NR3C2 differentially affect expression levels, increasing the susceptibility to SA in psychiatric patients with a history of CT.