Association of COMT rs4680 Genotype With Chronic Neuropathic Pain Experience in Patients With Sickle Cell Disease

Abstract

Purpose: The pain experience of patients with sickle cell disease (SCD) frequently consists of episodes of acute exacerbation. However, recent studies suggest that many patients who suffer from SCD have symptoms of chronic neuropathic pain. Additional research is needed to determine what role genotype plays in the patient's pain phenotype experience in SCD. The purpose of our project was to determine whether a catechol-O-methyltransferase (COMT) single nucleotide polymorphism (SNP), rs4680, was associated with the experience of chronic neuropathic pain in patients with SCD.

Design: Cross sectional study.

Method: In our study, 184 patients (98% African American, mean age 36.5 ± 11.6 years, 63% female) completed the Self-Reported Leeds Assessment of Neuropathic Symptoms and Signs (S-LANNS) and the Neuropathic Pain Symptom Inventory (NPSI) and provided blood samples for genotyping of the rs4680 SNP. We conducted a cross-sectional association study using a likelihood ratio test that compared a model with and without genotype as a predictor. We also used linear regression model to determine whether the Met allele was associated with pain in an additive model.

Result: 50% of the study participants had a Val/Val genotype, 41% had a Val/Met, and 9% had a MET/MET. Between the three rs4680 genotypes, the differences in the mean S-LANNS or NPSI scores were not statistically significant. The Met allele was also not significantly associated with neuropathic pain (S-LANNS p = .23; NPSI p = .73) in an additive SNP model.

Conclusion: Further studies with larger samples are needed to determine if the Met/Met genotype predisposes patients with SCD to neuropathic pain and if other polymorphisms in the COMT gene play a role in this process.

Keywords: Neuropathic pain; Sickle cell disease; rs4680 genotype.