title: Pharmacogenomics study on cadherin 2 network with regard to HIV infection and methadone treatment outcome.
abstract: Heroin dependent patients have a high incidence of HIV infection. In contrast to the gene expression method, we developed a systemic correlation analysis method built upon the results of pharmacogenomics study in a methadone maintenance treatment (MMT) cohort consisting of 344 Taiwanese heroin dependent patients. We identified genetic variants and their encoding proteins that may be involved with HIV infection and MMT treatment outcome. Cadherin 2 (CDH2) genetic determinants were identified through the genome-wide pharmacogenomic study. We found significant correlations among HIV infection status, plasma levels of CDH2, cytokine IL-7, ADAM10, and the treatment responses to methadone. Two single nucleotide polymorphisms located within CDH2 gene showed associations with blood pressure and plasma CDH2 concentration. Plasma concentration of CDH2 showed correlations with the level of cytokine IL-7, status of HIV infection, and urine morphine test result. Plasma level of IL-7 was correlated with corrected QT interval (QTc) and gooseflesh skin withdrawal symptom score, while level of ADAM10 was correlated with plasma concentrations of vitamin D metabolite, nicotine metabolite, and R-methadone. The results suggest a novel network involving HIV infection and methadone treatment outcome.
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Hsiang-Wei
authors.initials: HW
authors.lastname: Kuo
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Chia-Lung
authors.initials: CL
authors.lastname: Shih
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Jieh-Hen
authors.initials: JH
authors.lastname: Tsung
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Sheng-Wen
authors.initials: SW
authors.lastname: Liu
authors.affiliation: Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
authors.forename: Shih-Kai
authors.initials: SK
authors.lastname: Chu
authors.affiliation: Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
authors.forename: Hsin-Chou
authors.initials: HC
authors.lastname: Yang
authors.affiliation: Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.|Graduate Institute of Biostatistics, College of Public Health, China Medical University, Taichung, Taiwan.
authors.forename: Hsiao-Hui
authors.initials: HH
authors.lastname: Tsou
authors.affiliation: Department of Psychology, National Taiwan University, Taipei, Taiwan.
authors.forename: Zih-Hsiang
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, United States of America.|The Feinstein Institute for Medical Research, Hofstra Northwell School of Medicine at Hofstra University, Manhasset, New York, United States of America.
authors.forename: Andrew C H
authors.initials: AC
authors.lastname: Chen
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.|Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Liu
mesh_terms: D000072197:ADAM10 Protein / Q000097:blood; D000328:Adult; D053829:Amyloid Precursor Protein Secretases / Q000097:blood; D015703:Antigens, CD / Q000097:blood / Q000235:genetics*; D015820:Cadherins / Q000097:blood / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D003932:Heroin / Q000009:adverse effects; D006556:Heroin Dependence / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D015851:Interleukin-7 / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008691:Methadone / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009020:Morphine / Q000009:adverse effects; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D014807:Vitamin D / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; C508605:IL7 protein, human; D015851:Interleukin-7; D008565:Membrane Proteins; D014807:Vitamin D; D003932:Heroin; D009020:Morphine; D053829:Amyloid Precursor Protein Secretases; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human; D008691:Methadone