Evaluating Associations between Average Pain Intensity and Genetic Variation in People with Sickle Cell Disease: An Exploratory Study

Abstract

Background: Pain is one of the most common and deleterious symptoms experienced by individuals with sickle cell disease (SCD). There is a paucity of studies identifying potential genetic mechanisms of pain in this population.

Aim: Examine associations between 11 functional single nucleotide polymorphisms in 9 candidate genes with reports of average pain intensity in individuals with sickle cell disease.

Method: Cross-sectional analyses were performed on data and blood samples collected through the Duke SCD Implementation Consortium Registry. Participants were asked to rate their pain "on the average" using an 11-point numeric rating scale (0 = no pain; 10 = pain as bad as you can imagine). We genotyped 11 single nucleotide polymorphisms in 9 pain-related genes using TaqMan® Genotyping Assays. Associations between each polymorphism and reports of average pain were evaluated.

Results: The 86 participants (mean age: 28.7 years; 64% female) included in this study reported moderate pain on average (Mean = 4, Standard Deviation = 2.4). ICAM1 rs1799969 was the only genetic polymorphism that was significantly associated with pain (p = .01). Individuals with one or more minor alleles had lower average pain (Mean = 1.25, Standard Deviation = 1.50) than individuals without a minor allele (Mean = 4.13, Standard Deviation = 2.25). The effect size for ICAM1 rs1799969 was 1.30, which is considered large. The effect sizes for all other single nucleotide polymorphisms ranged from small to medium (range: 0-0.3).

Conclusions: Our findings provide preliminary evidence that the minor allele in ICAM1 rs1799969 had protective effects against experiencing more severe pain in sickle cell disease.

Keywords: genetic variation; pain; polymorphisms; sickle cell disease.