Concurrent Oral 3 – Genetics and Epidemiology [OP16–OP23]

Background: A genetic component to musculoskeletal pain aetiology has been reported but the genes involved are unknown. DREAM represses transcription of prodynorphin (PDYN), which encodes dynorphin, an endogenous ligand to the antinociceptive κ opioid receptor. A key role for DREAM in pain modulation has been demonstrated by hypoalgesia in DREAM knockout mice due to increased dynorphin expression and increased κ opioid tone. The aim of this study was to determine if, among individuals with pain, genetic variation in this pathway was associated with the number of bodily sites affected by musculoskeletal pain. Methods: Subjects 25-65 years old were recruited into a population-based cohort study (EPIFUND) from 3 primary-care registers in the North-West of England. At 3 time-points over 4 years, participants indicated the presence of musculoskeletal pain by shading blank body manikins on a postal questionnaire. At each time-point subjects received a score (0 to 29) indicating the number of pain sites shaded. From that data we used the highest number of pain sites reported at any time-point to create the outcome “number of pain sites”. Higher scores indicate more pain. DNA was available on 1189 participants. Pair-wise tag SNPs (r2 > 0.8) were selected for DREAM, PDYN and the κ opioid receptor (OPRK1) and their 10 kb flanks and genotyped using Sequenom. Zero-inflated negative binomial regression was used to test for association between SNPs and the number of pain sites. Results are reported as proportional change in the number of pain sites among subjects reporting pain (Rate Ratios (RR) and 95% CI). Results: Of the 39 SNPs selected, 35 were genotyped in 1055 subjects of which 83% reported pain. SNPs in all 3 genes were associated with the number of pain sites. Carriage of the common T allele of the DREAM SNP, rs4854253, was associated with reporting fewer pain sites (RR = 0.84 (0.72, 0.98) p = 0.029). This was also true for each copy of the minor C allele of rs11087273 in PDYN (RR = 0.85 (0.77, 0.95) p = 0.004) and carriage of the minor G allele of rs10504152 in OPRK1 (RR = 0.87 (0.77, 0.97) p = 0.014). To assess the combined effect of these SNPs, subjects were scored for the number (0-3) of genotypes associated with the outcome (TC or TT for rs4854253, TC or CC for rs11087273 and AG or GG for rs10504152). Seven per cent of subjects had 0 genotypes, 54% had 1, 33% had 2 and 7% had 3. With each additional genotype subjects reported fewer pain sites (RR = 0.87 (0