背景:遗传和环境因素在重度抑郁症(MDD)和自杀未遂(SA)的发展中起着至关重要的作用。然而,这两个项目之间的相互作用仍然未知。本研究旨在探讨患有MDD和SA的患者中5-羟色胺2A受体(HTR2A)和一氧化氮合酶1(NOS1)的遗传变异与环境因素之间的相互作用。
方法:共招募了334例MDD和有SA(MDD-SA)病史的MDD患者以及518例没有SA(MDD-NSA)病史的MDD患者,和716个健康对照(HC)。收集人口统计学数据和临床特征。Sequenom质谱用于检测HTR2A(rs1328683,rs17068986和rs3125)和NOS1(rs1123425,rs2682826,rs3741476,rs527590和rs7959232)中的八个标签单核苷酸多态性(tagSNPs)。使用广义多因子降维(GMDR)来分析基因-环境相互作用。
结果:四个标签SNP(rs17068986,rs3125,rs527590和rs7959232)在三组之间显示出显着差异。然而,Bonferroni校正后,MDD-SA组和MDD-NSA组之间的差异不显著.Logistic回归分析显示负性生活事件(OR=1.495,95CI:1.071-2.087,P=0.018)。自我负罪感(OR=2.263,95CI:1.515-3.379,P<0.001),阴性认知(OR=2.252,95CI:1.264~4.013,P=0.006)均与MDD患者SA独立相关。此外,GMDR分析表明HTR2Ars3125与负性生活事件之间存在显著的交互作用。与不存在与CC基因型相关的负性生活事件相比,与HTR2Ars3125CGGG基因型相关的负性生活事件与MDD患者的SA风险更高(OR=2.547,95%CI:1.264-5.131,P=0.009)。
结论:在SA和MDD患者中发现了几种危险因素以及HTR2Ars3125与负性生活事件之间的潜在相互作用。观察到的相互作用可能调节MDD和SA的风险,阐明MDD患者SA的发病机制。
BACKGROUND: Both genetic and environmental factors play crucial roles in the development of major depressive disorder (MDD) and suicide attempts (SA). However, the interaction between both items remains unknown. This
study aims to explore the interactions between the genetic variants of the serotonin 2 A receptor (HTR2A) and the nitric oxide synthase 1 (NOS1) and environmental factors in patients who experience MDD and SA.
METHODS: A total of 334 patients with MDD and a history of SA (MDD-SA) were recruited alongside 518 patients with MDD with no history of SA (MDD-NSA), and 716 healthy controls (HC). The demographic data and clinical characteristics were collected. Sequenom mass spectrometry was used to detect eight tag-single nucleotide polymorphisms (tagSNPs) in HTR2A (rs1328683, rs17068986, and rs3125) and NOS1 (rs1123425, rs2682826, rs3741476, rs527590, and rs7959232). Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-environment interactions.
RESULTS: Four tagSNPs (rs17068986, rs3125, rs527590, and rs7959232) exhibited significant differences between the three groups. However, these differences were not significant between the MDD-SA and MDD-NSA groups after Bonferroni correction. A logistic regression analysis revealed that negative life events (OR = 1.495, 95%CI: 1.071-2.087, P = 0.018), self-guilt (OR = 2.263, 95%CI: 1.515-3.379, P < 0.001), and negative cognition (OR = 2.252, 95%CI: 1.264-4.013, P = 0.006) were all independently associated with SA in patients with MDD. Furthermore, GMDR analysis indicated a significant interaction between HTR2A rs3125 and negative life events. Negative life events in conjunction with the HTR2A rs3125 CG + GG genotype were associated with a higher SA risk in patients with MDD when compared to the absence of negative life events in conjunction with the CC genotype (OR = 2.547, 95% CI: 1.264-5.131, P = 0.009).
CONCLUSIONS: Several risk factors and a potential interaction between HTR2A rs3125 and negative life events were identified in patients with SA and MDD. The observed interaction likely modulates the risk of MDD and SA, shedding light on the pathogenesis of SA in patients with MDD.