Birmingham Daniel J, Nagaraja H N, Rovin Brad H, Spetie Lacramioara, Zhao Yanxing, Li Xiaobai, Hackshaw Kevin V, Yu C Yung, Malarkey William B, Hebert Lee A
Ohio State University, Columbus, OH 43210, USA.
Arthritis Rheum. 2006 Oct;54(10):3291-9. doi: 10.1002/art.22135.
Stress is believed to be a risk factor for systemic lupus erythematosus (SLE) flare. Two serotonin-related gene polymorphisms, the serotonin receptor 1A (5-HT1A) polymorphism at -1019C>G and the serotonin transporter LS polymorphism, have been reported to affect stress-related behaviors. The purpose of this study was to assess the relationship between self-perceived stress (SPS), variability in SPS, and the 2 serotonin-related gene polymorphisms as risk factors for SLE flare.
Seventy-seven SLE patients (50 with lupus nephritis) were evaluated every 2 months (mean +/- SD total followup 18.5 +/- 8.5 months), and patients recorded their daily SPS levels (0-10 scale). Values for mean SPS and coefficient of variation (CV) for SPS were calculated from the 60-day block of daily measurements between study visits. Serotonin-related gene polymorphism genotypes were determined by polymerase chain reaction-based methods.
Of the 77 patients, 53 experienced 80 flares of SLE (32 renal flares) based on prespecified criteria. Multivariate analysis revealed that whereas neither the serotonin-related gene polymorphisms nor the mean SPS was predictive of an SLE flare, an increased CV for SPS was predictive (P = 0.0031). Interaction between the CV for SPS and the 5-HT1A -1019C>G polymorphism was also found to be a predictor of SLE flare (P = 0.0039). Subset analysis revealed that only in lupus nephritis patients were increasing CVs for SPS (P = 0.0002) and the interaction between CVs for SPS and 5-HT1A (P < 0.0001) predictive of a flare. Odds ratio curves demonstrated that the predictive effect of increasing CVs for SPS required the presence of the 5-HT1A -1019 G allele, but appeared to be independent of the G allele number.
Fluctuation in the level of SPS is a risk factor for the onset of flare in SLE patients with major renal manifestations when it occurs on the background of a stress-related susceptibility gene (the 5-HT1A -1019 G allele).
压力被认为是系统性红斑狼疮（SLE）病情复发的一个风险因素。据报道，两种与血清素相关的基因多态性，即-1019C>G位点的血清素受体1A（5-HT1A）多态性和血清素转运体LS多态性，会影响与压力相关的行为。本研究的目的是评估自我感知压力（SPS）、SPS的变异性与这两种与血清素相关的基因多态性作为SLE病情复发风险因素之间的关系。
对77例SLE患者（50例患有狼疮性肾炎）每2个月进行一次评估（平均随访时间±标准差为18.5±8.5个月），患者记录其每日的SPS水平（0-10分制）。根据研究访视期间60天的每日测量数据计算SPS的平均水平和变异系数（CV）。通过基于聚合酶链反应的方法确定与血清素相关的基因多态性基因型。
在这77例患者中，根据预先指定的标准，53例经历了80次SLE病情复发（32次肾脏病情复发）。多变量分析显示，与血清素相关的基因多态性和SPS的平均水平均不能预测SLE病情复发，但SPS的CV增加具有预测性（P = 0.0031）。还发现SPS的CV与5-HT1A -1019C>G多态性之间的相互作用是SLE病情复发的一个预测因素（P = 0.0039）。亚组分析显示，仅在狼疮性肾炎患者中，SPS的CV增加（P = 0.0002）以及SPS的CV与5-HT1A之间的相互作用（P < 0.0001）可预测病情复发。优势比曲线表明，SPS的CV增加的预测作用需要存在5-HT1A -1019 G等位基因，但似乎与G等位基因的数量无关。
当SPS水平的波动发生在与压力相关的易感基因（5-HT1A -1019 G等位基因）背景下时，它是具有主要肾脏表现的SLE患者病情复发的一个风险因素。
