Gamma‐aminobutyric acid transaminase genetic polymorphism is a candidate locus for responsiveness to opioid analgesics in patients with cancer pain: An exploratory study. Issue 4 (14th September 2018)

• Record Type: Journal Article
• Authors: Yokoshima, Yaeko; Sumitani, Masahiko; Nishizawa, Daisuke; Nagashima, Makoto; Ikeda, Kazutaka; Kato, Ryoji; Hozumi, Jun; Abe, Hiroaki; Azuma, Kenji; Tsuchida, Rikuhei; Yamada, Yoshitsugu
• Other Names: Ogawa Setsuro investigator.; Hattori Seiji investigator.; Takarada Junko investigator.; Fujiwara Yasuhiro investigator.; Hirose Munetaka investigator.; Hosokawa Toyoshi investigator.; Ueno Hiroshi investigator.; Mashimo Takashi investigator.; Saitoh Youichi investigator.; Matsuda Yoichi investigator.; Ueda Hiroshi investigator.; Yamauchi Teruo investigator.; Yamauchi Hideko investigator.; Shimojo Nobutake investigator.; Saitoh Shigeru investigator.; Yamada Makiko investigator.; Shimokawa Toshio investigator.; Ogata Toru investigator.
• Is Part Of: Neuropsychopharmacology reports. Volume 38:Issue 4(2018)
• Page Start: 175
• Page End: 181
• Publication Date: 2018-09-14
• Subjects: genetics: human -- pain: basic/clinical -- pharmacogenetics: basic/clinical -- responsiveness to opioid analgesics; Neuropsychopharmacology -- Periodicals; 615.78
• DOI: 10.1002/npr2.12030
• Languages: English
• ISSNs: 2574-173X

Abstract

Abstract: Aim: Cancer pain impairs not only physical functions but also social functions and roles. Consequently, the overall health‐related quality of life of patients with cancer pain deteriorates. Opioid analgesics are recommended for treating moderate to strong cancer pain. Advances in human genome research have fueled a growing interest to understand individual differences in responsiveness to opioid analgesics. This study aimed to explore and identify novel loci for genes predisposing an individual to opioid analgesic responsiveness. Methods: A total of 71 cancer patients rated their pain on an 11‐point numerical rating scale twice before and after increasing opioid analgesics. A genomewide association study focusing on single nucleotide polymorphisms (SNPs) was conducted to associate pain decrease with increased dosage of opioid analgesics based on weight (ie, responsiveness to opioid analgesics). A genomewide significance ( P < 5E‐8) was set for multiplicity of analyses to control for false positives. Results: Two SNPs passed the genomewide threshold for significance. One exonic SNP (rs1641025) was located in the ABAT [4‐aminobutyrate aminotransaminase (GABA transaminase)] gene on chromosome 16. The other SNP (rs12494691) was located on chromosome 3, which was not associated with any known genes. These SNPs were not associated with opioid‐related adverse effects. Conclusions: Our results preliminarily suggest that both SNPs might be potential candidate loci for responsiveness to opioid analgesics, and GABA transaminase might be a possible target for developing adjuvant pharmacotherapy with opioid analgesics in adjuvant pharmacotherapy. Our results should be validated in a large‐scale study with a larger sample size. Abstract : A genome‐wide association study revealed two candidate single nucleotide polymorphisms for responsiveness to opioid analgesics in patients with cancer pain, one of which locates on the GABA transaminase gene.