The role of CREB gene polymorphisms in the individual differences in sensitivity to addictive substances and vulnerability to dependence

2014 Fiscal Year Final Research Report

• Project/Area Number: 24790544
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: NISHIZAWA Daisuke 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 主任研究員 (80450584)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 薬物依存 / 薬物感受性 / 薬物感受性・依存症脆弱性個人差の遺伝要因 / 遺伝子多型 / サイクリックAMP応答配列結合タンパク質

Outline of Final Research Achievements

In association analyses for single nucleotide polymorphisms (SNPs) in and around the CREB3, CREB5, and ATF2 (CREB2) gene regions, only rs7583431 SNP flanking the ATF2 gene was significantly associated with the effect of opioid analgesic, fentanyl.
In additional association analyses, the C allele of the rs2952768 SNP, flanking the CREB1 gene, was associated with more analgesic requirements in patients who underwent abdominal surgery, just as observed in subjects who were scheduled to undergo cosmetic orthognathic surgery. Moreover, carriers of the C allele in this SNP exhibited less vulnerability to severe drug dependence in patients with methamphetamine dependence, alcohol dependence, and eating disorders and a lower “Reward Dependence” score on a personality questionnaire and higher Intelligence Quotient (IQ) score in two independent cohorts of healthy subjects. Furthermore, the C/C genotype of this SNP was significantly associated with the elevated mRNA expression of CREB1 gene.

Free Research Field

分子精神医学