@article{7d1c9ecd28854ccf8a989460ace5c928,
title = "Association between the catechol-O-methyltransferase Val158Met polymorphism and cocaine dependence",
abstract = "Dopaminergic brain systems have been documented to have a major role in drug reward, thus making genes involved in these circuits plausible candidates for susceptibility to substance use disorders. The catechol-O-methyltransferase (COMT) is involved in the degradation of catecholamines and a functional polymorphism (Val158Met) has been suggested to influence enzyme activity. In this study we hypothesize that genetic variation in the COMT gene contributes to increased risk for cocaine dependence. Cocaine-dependent individuals (n=330) and screened unaffected normal controls (n=255) were genotyped for three SNPs in the COMT gene (rs737865, rs4680 (Val158Met), rs165599). All cases and controls were of African descent. Genotype and allele frequencies differed significantly for the Val158Met polymorphism between cases (f(Met)=35%) and controls (f(Met)=27%) (p=0.004; corrected p=0.014; OR 1.44; 95% CI 1.12-1.86). Haplotype analysis showed a significant association for a two-marker haplotype rs737865-Val158Met (p=0.005). Results suggest that variation in COMT increases risk for cocaine dependence. The low enzyme activity 158Met allele or haplotypes containing this variant might have functional effects on dopamine-derived reward processes and cortical functions resulting in increased susceptibility for cocaine dependence. Additional studies are required to elucidate the role of COMT in the pathophysiology of substance use disorders.",
author = "Lohoff, {Falk W.} and Weller, {Andrew E.} and Bloch, {Paul J.} and Nall, {Aleksandra H.} and Ferraro, {Thomas N.} and Kampman, {Kyle M.} and Pettinati, {Helen M.} and Oslin, {David W.} and Dackis, {Charles A.} and O'Brien, {Charles P.} and Berrettini, {Wade H.}",
note = "Funding Information: This work was supported by the center for neurobiology and behavior, department of psychiatry, University of Pennsylvania. Financial support is gratefully acknowledged from national institutes of health grants MH59553, MH63876 (WHB), T32MH014654-29A1 (FWL), NIDA GRANTS P60-051186 (CPO) and P50-12756 (HMP), the VISN4 Mental Illness Research and Clinical Center grant from the Veterans Affairs Administration (DWO), grants from the National Alliance for Research on Schizophrenia and Depression (WHB), a grant from the Tzedakah Foundation (WHB), the Daland Fellowship Award by the American Philosophical Society (FWL), and a grant from Philip and Marcia Cohen (WHB). We thank Candice Schwebel for technical assistance. Most importantly, we thank the patients who participated in and contributed to these studies. The NIMH control subjects were collected by the NIMH Schizophrenia Genetics Initiative {\textquoteleft}Molecular Genetics of Schizophrenia II{\textquoteright} (MGS-2) collaboration. The investigators and co-investigators are: ENH/Northwestern University, Evanston, IL, MH059571FPablo V Gejman (collaboration coordinator; PI), Alan R Sanders; Emory University School of Medicine, Atlanta, GA, MH59587FFarooq Amin (PI); Louisiana State University Health Sciences Center, New Orleans, LA, MH067257FNancy Buccola APRN (PI); University of California, Irvine, Irvine, CA, MH60870FWilliam Byerley (PI); Washington University, St Louis, MO, U01, MH060879FC Robert Cloninger (PI); University of Iowa, Iowa, IA, MH59566FRaymond Crowe (PI), Donald Black; University of Colorado, Denver, CO, MH059565FRobert Freedman (PI); University of Pennsylvania, Philadelphia, PA, MH061675FDouglas Levinson (PI); University of Queensland, QLD, Australia, MH059588FBryan Mowry (PI); and Mt Sinai School of Medicine, New York, NY, MH59586FJeremy Silverman (PI).",
year = "2008",
month = dec,
doi = "10.1038/npp.2008.126",
language = "English (US)",
volume = "33",
pages = "3078--3084",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "13",
}