Fluctuation in self‐perceived stress and increased risk of flare in patients with lupus nephritis carrying the serotonin receptor 1A –1019 G allele

Abstract

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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).