Dopamine transporter gene (SLC6A3) polymorphism rs2963257 and chronic pain susceptibility in a Japanese population

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Introduction: Chronic pain exhibits significant interindividual variability, partly because of genetic factors. The dopaminergic system is implicated in pain modulation. Objectives: This study investigated the association between single-nucleotide polymorphisms (SNPs) in dopamine pathway genes and chronic pain susceptibility in a Japanese population. Methods: A case–control study compared 191 patients with chronic pain with 282 healthy controls in Japan. Genotype data from previous whole-genome studies were analyzed for SNPs within or flanking 8 candidate genes (tyrosine hydroxylase, solute carrier family 6 member 3 [ SLC6A3 ], dopamine D1–D5 receptor genes, and catechol-O-methyltransferase), including the gene body and ±30 kb flanking regions. Association analyses used Pearson chi-squared tests and modified Poisson regression with Bonferroni correction. Results: After quality control, 184 SNPs were analyzed. A significant association was identified between the rs2963257 SNP flanking the SLC6A3 gene and chronic pain (genotypic P = 0.00026). This remained significant after Bonferroni correction. Analysis using a dominant model for the A allele (GA + AA vs GG) also showed a significant association (prevalence ratio = 2.11, 95% confidence interval = 1.23–3.61, P = 0.0017), indicating individuals carrying at least one A allele had a significantly higher prevalence of chronic pain vs those with the GG genotype. No other SNPs showed a significant association after multiple comparison correction. Conclusions: The SLC6A3 rs2963257 polymorphism is associated with chronic pain susceptibility in the Japanese population. Specifically, the A allele appears to increase susceptibility under a dominant model, suggesting the GG genotype may have a protective effect against chronic pain.