Hansen Ebba Holme², Plessen Kerstin Jessica¹, Rasmussen Henrik Berg³, Anne Katrine Pagsberg¹, and The INDICES Consortium⁵*
¹ Child and Adolescent Mental Health Center, Mental Health Services Capital Region of Denmark and Department of Clinical Medicine, University of Copenhagen, Denmark
² Department of Pharmacy, Section for Clinical and Social Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
³ Copenhagen University Hospital, Capital Region of Denmark, Mental Health Centre Sct. Hans, Institute of Biological Psychiatry, Denmark
? Roskilde University Hospital, Unit of Clinical Pharmacology, Denmark
? List of all partners in INDICES Consortium: Henrik Berg Rasmussen, Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark;DitteBjerre, Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark;Majbritt Busk Madsen, Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark; Laura Ferrero, Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark;Kristian Linnet, Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark;Ragnar Thomsen, Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark; GescheJürgens, Roskilde University Hospital, Unit of Clinical Pharmacology, Denmark; Kim Dalhoff, Department of Clinical Pharmacology, Bispebjerg University Hospital, Copenhagen, Denmark; Claus Stage, Department of Clinical Pharmacology, Bispebjerg University Hospital, Copenhagen, Denmark;Hreinn Stefansson, CNS Division, deCODE Genetics, Reykjavik, Iceland;Thomas Hankemeier, The Leiden/Amsterdam Center for Drug Research LACDR, Leiden University, Gorlaeus laboratories, Leiden, The Netherlands;Rima Kaddurah-Daouk, Department of Psychiatry and Behavioural Sciences, Duke University, Durham, NC, USA;SørenBrunak, Center for Biological Sequence Analysis, Technical University of Denmark, Kgs. Lyngby, Denmark;Olivier Taboureau, Center for Biological Sequence Analysis, Technical University of Denmark, Kgs. Lyngby, Denmark;Grace Shema Nzabonimpa, Center for Biological Sequence Analysis, Technical University of Denmark, Kgs. Lyngby, Denmark;Tine Houmann, Centre for Child and Adolescent Mental Health, Mental Health Services in the Capital Region of Denmark; Pia Jeppesen, Centre for Child and Adolescent Mental Health, Mental Health Services in the Capital Region of Denmark; Kristine Kaalund-Jørgensen, Centre for Child and Adolescent Mental Health, Mental Health Services in the Capital Region of Denmark;Peter Riis Hansen, Department of Cardiology, Copenhagen University Hospital, Hellerup, Denmark; Karl Emil Kristensen, Department of Cardiology, Copenhagen University Hospital, Hellerup, Denmark;Anne Katrine Pagsberg, Centre for Child and Adolescent Mental Health, Mental Health Services in the Capital Region of Denmark; Kerstin J Plessen, Centre for Child and Adolescent Mental Health, Mental Health Services in the Capital Region of Denmark;. Poul-Erik Hansen, Department of Science, Systems and Models, Roskilde University, Roskilde, Denmark; Thomas Werge, Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark; JørgenDyrborg, Centre for Child and Adolescent Mental Health, Mental Health Services in the Capital Region of Denmark; Maj-Britt Lauritzen, Centre for Child and Adolescent Mental Health, Mental Health Services in the Capital Region of Denmark
Corresponding Author:
Anne Katrine Pagsberg, Research Unit, Child and Adolescent Mental Health Center, Mental Health Services Capital Region of Denmark & Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Tel. +4538641180; Fax +4538644487; Email: anne.katrine.pagsberg@regionh. dk
Abstract
Children with Attention Deficit Hyperactivity Disorder (ADHD) show large variations in response to methylphenidate (MPH) treatment, which may result from genetic factors associated with MPH metabolism. We aimed at investigating a possible link between the -75 T>G polymorphism in the 5’ untranslated region of the gene coding for carboxylesterase 1 (CES1) and a common adverse effect, weight loss, during the first three months of MPH treatment.
We analyzed the association between a CES1 polymorphism and longitudinal clinical data based on retrospective analysis of medical records, from first to last recorded visit at the clinic. By use of poly chain reaction and the Sanger method we genotyped the -75 T>G gene polymorphism and examined the association to clinical response, which was based on retrospective analysis of longitudinal clinical data from medical records. The primary clinical outcome measure was weight loss during the first 3 months of MPH treatment.
Data from 74 MPH treated children with ADHD, mean age 8.6 years, 57% males, were analysed. There were n=26 G-carriers (heterozygote TG and homozygote GG) and n=48 TT-homozygotes. The proportion of weight loss and mean weight change differed significantly in G-carriers (88% / -0.279 kg) compared with TT-homozygotes (31% / +0.157 kg). This study shows an association between the -75 T>G polymorphism in CES1 and MPH treatment response, demonstrated by a significantly higher frequency and extent of weight loss in G-carriers compared to TT-homozygotes.
Citation
Oxenbøll M, Kaalund-Jørgensen K, Rasmussen S, Bjerre D, Jürgens G, Hansen EH, et al. Association of Carboxylesterase 1 Gene (CES1) Polymorphism with Weight Loss in Children with Attention Deficit Hyperactivity Disorder during Methylphenidate Treatment. SM J Bioinform Proteomics. 2017; 2(1): 1010.
