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

Authors

Keiko Yamada, Daisuke Nishizawa, Hideko Arita, Kazuo Hanaoka, Choku Yajima, Jitsu Kato, Setsuro Ogawa, Ayako Hiranuma, Junko Hasegawa, Yuko Ebata, Kyoko Nakayama, Masako Iseki, Kazutaka Ikeda

Published in

Pain reports. Volume 11. Issue 4. Pages e1478. Epub Jul 16, 2026.

Abstract

Chronic pain exhibits significant interindividual variability, partly because of genetic factors. The dopaminergic system is implicated in pain modulation.
This study investigated the association between single-nucleotide polymorphisms (SNPs) in dopamine pathway genes and chronic pain susceptibility in a Japanese population.
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.
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.
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.

PMID:
42491814
Bibliographic data and abstract were imported from PubMed on 24 Jul 2026.

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