Buji R I, Abdul Murad N A, Chan L F, Maniam T, Mohd Shahrir M S, Rozita M, Shamsul A S, Mohamad Hussain R, Abdullah N, Jamal R, Nik Jaafar N R
1 Hospital Mesra Bukit Padang, Kota Kinabalu, Sabah, Malaysia.
2 UKM Medical Molecular Biology Institute (UMBI), Kuala Lumpur, Malaysia.
Lupus. 2018 Apr;27(5):744-752. doi: 10.1177/0961203317742711. Epub 2017 Nov 21.
Background Systemic lupus erythematosus (SLE) patients are a high-risk population for suicide. Glutamatergic neurosystem genes have been implicated in the neurobiology of depression in SLE and suicidal behaviour in general. However, the role of glutamate receptor gene polymorphisms in suicidal behaviour among SLE patients remains unclear in the context of established clinical and psychosocial factors. We aimed to investigate the association of NR2A gene polymorphism with suicidal ideation in SLE while accounting for the interaction between clinical and psychosocial factors. Methods A total of 130 SLE patients were assessed for mood disorders (MINI International Neuropsychiatric Interview), severity of depression (Patient Health Questionnaire-9), suicidal behaviour (Columbia-Suicide Severity Rating Scale), socio-occupational functioning (Work and Social Adjustment Scale), recent life events (Social Readjustment Rating Scale) and lupus disease activity (SELENA-SLE Disease Activity Index). Eighty-six out of the 130 study participants consented for NR2A genotyping. Results Multivariable logistic regression showed nominal significance for the interaction effect between the NR2A rs2072450 AC genotype and higher severity of socio-occupational impairment with lifetime suicidal ideation in SLE patients ( p = 0.038, odds ratio = 1.364, 95% confidence interval = 1.018-1.827). However, only the association between lifetime mood disorder and lifetime suicidal ideation remained significant after Bonferroni correction ( p < 0.001, odds ratio = 33.834, 95% confidence interval = 7.624-150.138). Conclusions Lifetime mood disorder emerged as a more significant factor for suicidal ideation in SLE compared with NR2A gene polymorphism main and interaction effects. Clinical implications include identification and treatment of mood disorders as an early intervention for suicidal behaviour in SLE. More adequately-powered gene-environment interaction studies are required in the future to clarify the role of glutamate receptor gene polymorphisms in the risk stratification of suicidal behaviour among SLE patients.
系统性红斑狼疮（SLE）患者是自杀的高危人群。谷氨酸能神经系统基因与SLE患者的抑郁神经生物学及一般自杀行为有关。然而，在既定的临床和社会心理因素背景下，谷氨酸受体基因多态性在SLE患者自杀行为中的作用仍不清楚。我们旨在研究NR2A基因多态性与SLE患者自杀意念之间的关联，同时考虑临床和社会心理因素之间的相互作用。方法：对130例SLE患者进行了情绪障碍评估（迷你国际神经精神访谈）、抑郁严重程度评估（患者健康问卷-9）、自杀行为评估（哥伦比亚自杀严重程度评定量表）、社会职业功能评估（工作和社会适应量表）、近期生活事件评估（社会再适应评定量表）以及狼疮疾病活动度评估（SELENA-SLE疾病活动指数）。130名研究参与者中有86名同意进行NR2A基因分型。结果：多变量逻辑回归显示，NR2A rs2072450 AC基因型与较高的社会职业功能损害严重程度之间的交互作用对SLE患者终生自杀意念具有名义显著性（p = 0.038，比值比 = 1.364，95%置信区间 = 1.018 - 1.827）。然而，在Bonferroni校正后，仅终生情绪障碍与终生自杀意念之间的关联仍然显著（p < 0.001，比值比 = 33.834，95%置信区间 = 7.624 - 150.138）。结论：与NR2A基因多态性的主要效应和交互效应相比，终生情绪障碍是SLE患者自杀意念更显著的因素。临床意义包括将情绪障碍的识别和治疗作为SLE患者自杀行为的早期干预措施。未来需要开展更有充分统计学效力的基因-环境相互作用研究，以阐明谷氨酸受体基因多态性在SLE患者自杀行为风险分层中的作用。
