title: Association between KCNJ6 (GIRK2) gene polymorphism rs2835859 and post-operative analgesia, pain sensitivity, and nicotine dependence.
abstract: G-protein-activated inwardly rectifying potassium (GIRK) channels are expressed in many tissues and activated by several Gi/o 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.
authors.affiliation: Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nishizawa
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Fukuda
authors.forename: Shinya
authors.initials: S
authors.lastname: Kasai
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Ogai
authors.forename: Junko
authors.initials: J
authors.lastname: Hasegawa
authors.forename: Naomi
authors.initials: N
authors.lastname: Sato
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yamada
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Tanioka
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
authors.forename: Masakazu
authors.initials: M
authors.lastname: Hayashida
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ikeda
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D017288:Pain Threshold; D010149:Postoperative Pain / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000235:genetics; D016540:Smoking Cessation; D000074606:Smoking Prevention; D014029:Tobacco Use Disorder / Q000235:genetics* / Q000628:therapy; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C094401:KCNJ6 protein, human