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October 13, 2012
8:00:00 AM - 9:30:00 AM
Room 103A
FKBP5 Variants Predict Neck Pain Persistence 6 Weeks After Motor Vehicle Collision
Jennifer Smith, B.S., Jacob Ulirsch, B.S., Andrey Bortsov, M.D.,Ph.D., Robert Swor, D.O., David Peak, M.D., Jeffrey Jones, M.D., Niels Rathlev, M.D., Luda Diatchenko, M.D.,Ph.D., Samuel McLean, M.D.,M.P.H.
UNC-Chapel Hill, Chapel Hill, North Carolina, United States
AIMS OF INVESTIGATION: Several lines of evidence suggest that physiologic systems involved in the stress response may contribute to the development of whiplash-associated disorders (WAD). If this is the case, then genetic variants influencing stress system function should predict WAD outcomes. The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system of central importance to the stress response. FK506 binding protein 5 (FKBP5), a chaperone protein for the glucocorticoid receptor (GR), influences HPA axis function. FKBP5 variants have been associated with posttraumatic stress disorder vulnerability in gene x environment interactions. In this study, we examined the association between FKBP5 variants and the presence of moderate to severe neck pain and number of regions with persistent body pain six weeks following minor motor vehicle collision (MVC).

METHODS: European Americans ≥18 years of age who presented to the emergency department (ED) for care after MVC and were without injuries requiring hospital admission were recruited. Blood for DNA analysis was collected (PAXgene DNA tube) and participants were genotyped (Sequenom) at twenty-five tag SNPs chosen to cover haplotype diversity at the FKBP5 locus. Participants completed follow-up evaluations six weeks after MVC. Pain was assessed via 0-10 numeric rating scale (NRS) in each of the non-overlapping body regions of the Regional Pain Scale (RPS), with the addition of "head" as the 20th pain region. Moderate to severe neck pain (MSNP, defined as neck pain ≥4 on a 0-10 NRS) and total body areas with pain (TBAWP, defined as the number of body regions with pain >0) were calculated. Associations between FKBP5 polymorphisms and MSNP and TBAWP were determined using a logistic regression model in SAS (JMP interface), adjusting for participant age, sex, and ED site. Significance (alpha=0.005) was determined using spectral decomposition (SD) to account for multiple comparisons.

RESULTS: 9339 MVC patients were screened, 1584 were eligible, 949 were enrolled, and 838 have been genotyped. A dominant genetic model provided the best fit to the data, with nine SNPs (rs2395634, rs2817032, rs3800373, rs4713904, rs7751598, rs9368878, rs9380526, rs9394309, and rs9394314) demonstrating significant association with both MSNP and TBAWP outcomes after adjustment. The three SNPs with the strongest association with the outcomes of interest are reported in detail: (MA= minor allele, MAF=minor allele frequency) rs4713904 (MA=C, MAF=0.307, MSNP p=0.000007; 43% v. 29%, TBAWP p=0.00040; 5.6 v. 4.4 (CT/CC v. TT)), rs9394309 (MA=G, MAF=0.308, MSNP p=0.00048; 43% v. 29%, TBAWP p=0.00018; 5.6 v. 4.4 (GA/GG vs. AA)), and rs9380526 (MA=C, MAF=0.337, MSNP p=0.000062; 42% v. 29%, TBAWP p=0.00010; 5.6 v. 4.3 (CT/CC v. TT)).

CONCLUSION: FKBP5 variants predict pain outcomes six weeks after minor MVC.

Copyright © 2012 American Society of Anesthesiologists