(280) Interleukin 1alpha rs1800587 associates with chronic non-crisis pain in sickle cell disease

Abstract

Pain is prevalent in sickle cell disease (SCD) patients who display great heterogeneity in pain severity and frequency. Studying the contribution of relevant candidate gene polymorphisms may shed light on the etiology of the pain heterogeneity, allowing for precision pain medicine in SCD. We hypothesize that inflammatory factors are involved in the pathogenesis of sickle cell pain. In this study, we focused on the IL1A C/T polymorphism rs1800587 that is a single nucleotide polymorphism (SNP) located at position -889. The SNP came to our attention because our bioinformatic analysis predicted that this SNP is located in a cis-transcriptional regulatory region modulating the protein expression level. Pain phenotype data were gathered from PAINReportIt, a pain assessment tool for multidimensional pain experience. The composite pain index (CPI) was used as a measurement for the baseline pain. Utilization of urgent or emergency care due to sickling pain crisis was used as a surrogate for acute pain crisis in SCD. We found the T allele was associated with increased CPI. In our SCD cohort, each T allele was associated with a 3.9 increase in CPI (p=0.04), accounting for 3% of variability in CPI as determined by the additive multiple linear regression. We did not find significant association between this SNP and the patient utilization due to acute pain. These results represent the first indication that IL1A rs1800587 may influence the chronic non-crisis pain in SCD. This study was supported in part by grants from NIH (R01 HL124945, R01 HL098141 and T32DE018381).