Association Between KCNJ6 (GIRK2) Gene Polymorphism rs2835859 and Post-operative Analgesia, Pain Sensitivity, and Nicotine Dependence

作者：Nishizawa Daisuke; Fukuda Ken ichi; Kasai Shinya; Ogai Yasukazu; Hasegawa Junko; Sato Naomi; Yamada Hidetaka; Tanioka Fumihiko; Sugimura Haruhiko; Hayashida Masakazu; Ikeda Kazutaka^*

来源：Journal of Pharmacological Sciences, 2014, 126(3): 253-263.

DOI：10.1254/jphs.14189FP

• G-protein-activated inwardly rectifying potassium (GIRK) channel
• single-nucleotide polymorphism
• opioid analgesia
• pain
• susceptibility to nicotine dependence

G-protein-activated inwardly rectifying potassium (GIRK) channels are expressed in many tissues and activated by several Gib, protein coupled receptors, such as opioid and dopamine receptors, and thus are known to be involved in the modulation of opioid-induced analgesia, pain, and reward. We focused on a GIRK-channel subunit that plays a pivotal role in the brain, GIRK2, and investigated the contribution of genetic variations of the GIRK2 (KCNJ6) gene to individual differences in the sensitivity to opioid analgesia. In our initial linkage disequilibrium analysis, a total of 27 single-nucleotide polymorphisms (SNPs) were selected within and around the regions of the KCNJ6 gene. Among them, the rs2835859 SNP, for which associations with analgesia and pain have not been previously reported, was selected in the exploratory study as a potent candidate SNP associated with opioid analgesic sensitivity. The results were corroborated in further confirmatory study. Interestingly, this SNP was also found to be associated with sensitivity to both cold and mechanical pain, susceptibility to nicotine dependence, and successful smoking cessation. The results indicate that this SNP could serve as a marker that predicts sensitivity to analgesic and pain and susceptibility to nicotine dependence.

• 出版日期2014-11
• 单位河北医科大学