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


CONCLUSIONS
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).
Birmingham
Daniel J
DJ
Ohio State University, Columbus, OH 43210, USA. dan.birmingham@osumc.edu
Nagaraja
H N
HN
Rovin
Brad H
BH
Spetie
Lacramioara
L
Zhao
Yanxing
Y
Li
Xiaobai
X
Hackshaw
Kevin V
KV
Yu
C Yung
CY
Malarkey
William B
WB
Hebert
Lee A
LA
D000328:Adult; D000483:Alleles; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics / Q000523:psychology; D006801:Humans; D008181:Lupus Nephritis / Q000150:complications / Q000235:genetics* / Q000523:psychology*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010465:Perception; D011110:Polymorphism, Genetic; D011985:Receptors, Serotonin / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D012649:Self Concept; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological
D011985:Receptors, Serotonin; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins