Examining SLC6A4 Variations in the PRECISION Pain Research Registry




Phillips, Nicole R.
Lopez, Jonathan
Aryal, Subhash
Licciardone, John C.


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Purpose: Chronic low back pain is the leading cause of disability globally and has been linked to comorbidities such as depression. Common pathways involving serotonin and norepinephrine may play a role in both pain and mood disorders. The SLC6A4 gene, encoding a serotonin reuptake transporter, has been heavily studied with regard to depression. Polymorphisms within the gene are thought to influence the expression of the transporter, thereby modulating serotonin transmission. More recently, this gene has been studied in the context of chronic pain. This study seeks to further our understanding of chronic pain with respect to depression and other outcome measures in participants with chronic low back pain to aid in the development of better treatments. Methods: Participants with chronic low back pain in the PRECISION Pain Research Registry provided DNA samples that were genotyped on the Infinium Global Screening Array (Illumina). Long and short length polymorphisms of the SLC6A4 gene were predicted using an eight single nucleotide polymorphism (SNP) machine learning model. Of the eight, one SNP was collected from the array, and the other seven were imputed. Additionally, the rs25531A [greater than] G SNP was imputed. Using the length of the polymorphism and the rs25531 SNP, subjects were divided into high, intermediate and low expression groups. Participants also reported clinical status measures such as low back pain intensity, back-specific functioning, PROMIS quality of life, levels of pain self-efficacy, and pain catastrophizing. Results: There was no significant association between self-reported depression and expression levels (high, intermediate, low) of SLC6A4. No correlation was found between PROMIS depression scores and SLC6A4 expression. Analyses for depression values were conducted using logistic linear regression and non-parametric ANOVA respectively. There were no observed correlations between transporter expression level and the outcome variables of back-related disability, pain, pain catastrophizing, or pain self-efficacy. Disability was analyzed using ANOVA. Pain, pain catastrophizing, and pain self-efficacy were investigated using non-parametric ANOVA analyses. Conclusion: No correlations were found between serotonin transporter expression level and depression or other outcome variables. Similar previous studies investigating SLC6A4 used homogenous populations. We recommend conducting a larger study that takes into account race.