Association between the rs7583431 single nucleotide polymorphism close to the activating transcription factor 2 gene and the analgesic effect of fentanyl in the cold pain test

BACKGROUND: Activating transcription factor 2 (ATF2) is a member of the leucine zipper family of DNA binding proteins and is widely distributed in tissues. Several recent studies have demonstrated that this protein is involved in mechanisms that are related to pain and inflammation. However, unclear is whether polymorphisms of the ATF2 gene, which encodes the human ATF2 protein, influence pain or analgesic sensitivity. This study examined associations between the analgesic effect of fentanyl in the cold pressor-induced pain test and polymorphisms in the ATF2 gene in 355 Japanese subjects. RESULTS: In this study, 33 single nucleotide polymorphisms (SNPs) were selected, and a total of 2 linkage disequilibrium blocks with 6 Tag SNPs (rs1153702, rs7583431, rs2302663, rs3845744, rs268214, and rs1982235) were observed in the region within and around the ATF2 gene. We further analyzed associations between these Tag SNPs and clinical data. Even after multiple testing with Bonferroni adjustments, an increase in the analgesic effect of fentanyl in the cold pressor-induced pain test was significantly associated with a greater number of the A allele of the rs7583431 SNP (linear regression, P = .001). CONCLUSIONS: The present findings may contribute to adequate pain relief in individual patients. Although more research on the genetic factors that influence opioid sensitivity is needed, analgesic requirements may be predicted by analyzing ATF2SNPs, together with other polymorphisms of genes that are reportedly associated with opioid sensitivity, such as CREB1, OPRM1, and GIRK2.