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

Arthritis Rheum. 2006 Oct;54(10):3291-9. doi: 10.1002/art.22135.


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).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alleles
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genetic Predisposition to Disease / psychology
  • Humans
  • Lupus Nephritis / complications
  • Lupus Nephritis / genetics*
  • Lupus Nephritis / psychology*
  • Male
  • Middle Aged
  • Odds Ratio
  • Perception
  • Polymorphism, Genetic
  • Receptors, Serotonin / genetics*
  • Receptors, Serotonin / metabolism
  • Risk Factors
  • Self Concept*
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Stress, Psychological*


  • Receptors, Serotonin
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins