Genome-wide association study identifies a potent locus associated with human opioid sensitivity

• DOI: 10.1038/mp.2012.164
• Publication Date: 2012-11-27T09:05:00Z
• Authors: D Nishizawa; K Fukuda; S Kasai; J Hasegawa; Y Aoki; A Nishi; N Saita; Y Koukita; M Nagashima; R Katoh; Y Satoh; M Tagami; S Higuchi; H Ujike; N Ozaki; T Inada; N Iwata; I Sora; M Iyo; N Kondo; M-J Won; N Naruse; K Uehara-Aoyama; M Itokawa; M Koga; T Arinami; Y Kaneko; M Hayashida; K Ikeda
• Keywords: Genome-wide Association Study; Linkage Disequilibrium; Candidate gene; SNP

Opioids, such as morphine and fentanyl, are widely used effective analgesics for the treatment of acute chronic pain. In addition, opioid system has a key role in rewarding effects morphine, ethanol, cocaine various other drugs. Although sensitivity is well known to vary among individual subjects, several candidate genetic polymorphisms reported so far not sufficient fully understanding wide range interindividual differences human sensitivity. By conducting multistage genome-wide association study (GWAS) healthy we found that within linkage disequilibrium block spans 2q33.3–2q34 were strongly associated with requirements postoperative after painful cosmetic surgery. The C allele best single-nucleotide polymorphism (SNP), rs2952768, was more analgesic requirements, consistent results obtained patients who underwent abdominal carriers this SNP exhibited less vulnerability severe drug dependence methamphetamine dependence, alcohol eating disorders lower 'Reward Dependence' score on personality questionnaire subjects. Furthermore, C/C genotype significantly elevated expression neighboring gene, CREB1. These show SNPs locus most potent factors date, affecting both efficacy liability substance dependence. Our findings provide valuable information personalized pain