PT636. Association between the rs7583431 single-nucleotide polymorphism close to the activating transcription factor 2 (ATF2) gene and the analgesic effect of fentanyl in the preoperative cold pressor-induced pain test

Abstract

Background: Activating transcription factor 2 (ATF2) is a member of the leucine zipper family of DNA-binding proteins and is wildly distributed in tissues. Several recently studies have demonstrated that this protein is involved in mechanisms related to pain and inflammation. However, polymorphisms of the ATF2 gene is unclear that encodes the human ATF2 influence pain sensitivity. The ATF2 gene is known to be highly polymorphic. Thus the present study examined associations between the analgesic effect of fentanyl in the preoperative cold pressor-induced pain test and polymorphisms in the ATF2 gene in 355 Japanese patients who underwent orthognathic surgery.

Result: In the present study, 39 single nucleotide polymorphisms (SNPs) were polymorphic, and a total of 2 linkage disequilibrium blocks with 7 Tag SNPs (rs1153711, rs1153702, rs7583431, rs2302663, rs3845744, rs1205399, and rs268214) were observed in the region within and around the ATF2 gene. Thus, we further analyzed associations between these Tag SNPs and clinical data. Result of multiple testing such as Bonferroni adjustments, for the rs7583431 SNP, the analgesic effect of fentanyl in the preoperative cold pressor-induced pain test of the subjects in the AA group was significantly greater than in the AC + CC group (Mann-Whitney U-test, P = 0.007).

Conclusions: The present findings may contribute to adequate postoperative pain relief in individual patients. Although more research on the genetic factors that influence opioid sensitivity is necessary, postoperative analgesic requirements may be predicted before surgery by analyzing the ATF2 SNP, together with other polymorphisms in the genes that are reportedly associated with opioid sensitivity, such as OPRM1 and GIRK2.