OBJECTIVE AND METHODS: 5-Hydroxytryptamine (serotonin) receptor 2B (HTR2B) is involved in brain development. Although expressed in the human brain, HTR2B has not been investigated much for its role in higher brain functions. Here we describe a genome-scan with 391 simple sequence repeat markers in 300 Caucasians, identifying HTR2B gene as a candidate for drug abuse vulnerability. RESULTS: From DNA re-sequencing of 110 subjects, we discovered three novel single nucleotide polymorphisms (SNPs), two of which confer a double-mutant of the receptor protein in a drug-abusing population. Arg6, a conserved basic residue, and the conserved acidic Glu42 are mutated simultaneously into Gly, termed R6G/E42G. Furthermore, this double-mutant tends to associate with drug abuse (P = 0.08 by chi2 test). The third SNP that is a synonymous mutation in the codon of Gln11 showed significant association with drug abuse (P = 0.0335 by Fisher's exact test). CONCLUSION: Our data are the first suggesting that HTR2B contributes to brain architecture and pathways that are involved in illegal drug reward.
OBJECTIVE AND METHODS: 5-Hydroxytryptamine (serotonin) receptor 2B (HTR2B) is involved in brain development. Although expressed in the human brain, HTR2B has not been investigated much for its role in higher brain functions. Here we describe a genome-scan with 391 simple sequence repeat markers in 300 Caucasians, identifying HTR2B gene as a candidate for drug abuse vulnerability. RESULTS: From DNA re-sequencing of 110 subjects, we discovered three novel single nucleotide polymorphisms (SNPs), two of which confer a double-mutant of the receptor protein in a drug-abusing population. Arg6, a conserved basic residue, and the conserved acidic Glu42 are mutated simultaneously into Gly, termed R6G/E42G. Furthermore, this double-mutant tends to associate with drug abuse (P = 0.08 by chi2 test). The third SNP that is a synonymous mutation in the codon of Gln11 showed significant association with drug abuse (P = 0.0335 by Fisher's exact test). CONCLUSION: Our data are the first suggesting that HTR2B contributes to brain architecture and pathways that are involved in illegal drug reward.
Authors: Arpana Agrawal; Anthony L Hinrichs; Gerald Dunn; Sarah Bertelsen; Danielle M Dick; Scott F Saccone; Nancy L Saccone; Richard A Grucza; Jen C Wang; C Robert Cloninger; Howard J Edenberg; Tatiana Foroud; Victor Hesselbrock; John Kramer; Kathleen K Bucholz; Samuel Kuperman; John I Nurnberger; Bernice Porjesz; Marc A Schuckit; Alison M Goate; Laura J Bierut Journal: Drug Alcohol Depend Date: 2007-10-17 Impact factor: 4.492
Authors: Timothy S Kountz; Kyung-Soon Lee; Stacey Aggarwal-Howarth; Elizabeth Curran; Ji-Min Park; Dorathy-Ann Harris; Aaron Stewart; Joseph Hendrickson; Nathan D Camp; Alejandro Wolf-Yadlin; Edith H Wang; John D Scott; Chris Hague Journal: J Biol Chem Date: 2016-07-05 Impact factor: 5.157
Authors: Laura Bevilacqua; Stéphane Doly; Jaakko Kaprio; Qiaoping Yuan; Roope Tikkanen; Tiina Paunio; Zhifeng Zhou; Juho Wedenoja; Luc Maroteaux; Silvina Diaz; Arnaud Belmer; Colin A Hodgkinson; Liliana Dell'osso; Jaana Suvisaari; Emil Coccaro; Richard J Rose; Leena Peltonen; Matti Virkkunen; David Goldman Journal: Nature Date: 2010-12-23 Impact factor: 49.962
Authors: Laura R Lander; Vincent Setola; Shane W Kaski; Stephan Brooks; Sijin Wen; Marc W Haut; David P Siderovski; James H Berry Journal: J Opioid Manag Date: 2019 Mar-Apr