Single nucleotide polymorphisms associated with pain in sickle cell disease

Abstract

Pain is a major concern of patients with sickle cell disease (SCD). SCD pain is characterized by episodes of acute pain that are responsible for the majority of acute care utilization by SCD patients and persistent chronic pain that affects the quality of life in these patients. Acute care utilization is associated with SCD severity and pain. Pain severity and frequency vary significantly in SCD patients and we hypothesized that genetic polymorphisms would account for some of these variations. In the study, we applied the candidate gene approach to examine the role of single nucleotide polymorphisms (SNPs) in SCD pain. Sickle cell subjects (N=76; mean age=35; 67% female; 80% SS type) were recruited during routine outpatient clinic visits and entered answers to a computerized pain questionnaire (PAINReportIt-®), from which composite pain index (CPI) scores were calculated. Blood or buccal swab samples were collected for DNA extraction and genotyping was completed using PCR-RFLP, Taqman, and the Sequenom MassArray System. Data were analyzed using Pearson's chi-square or Fisher's exact tests followed by Bonferroni for multiplicity. Several SNPs were significantly associated with CPI scores, acute care utilization or opioid equivalent doses. One such association showed a relationship between DRD3 rs6280 and acute care utilization. Patients who did not have any acute care utilization within the year after providing the pain assessment were more likely to carry the heterozygote genotype. DRD3 rs6280 has been implicated in several pain models conferring its role in opioid therapy for pain in humans. These data suggest that genetic polymorphisms may account for some of the pain variations seen in SCD. The study was supported in part by grants from NIH (R01 HL078536, R01 HL098141) and the Illinois Department of Public Health (IDPH).