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Alcohol and Alcoholism Advance Access originally published online on August 10, 2004
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Alcohol & Alcoholism Vol. 39, No. 5, pp. 380-385, 2004
Alcohol & Alcoholism Vol. 39, No. 5 © Medical Council on Alcohol 2004; all rights reserved

ANALYSIS OF 5-HYDROXYTRYPTAMINE 2C RECEPTOR GENE PROMOTER VARIANTS AS ALCOHOL-DEPENDENCE RISK FACTORS

Salim Mottagui-Tabar1, Shane McCarthy1, Jana Reinemund1, Björn Andersson1, Claes Wahlestedt1 and Markus Heilig2,*

1 Center for Genomics and Bioinformatics and 2 Department of Clinical Neuroscience, Division of Psychiatry, Karolinska Institutet, Stockholm, Sweden

* Author to whom correspondence should be addressed at: Karolinska Institutet, Neurotec Department, Division of Psychiatry, Huddinge University Hospital, M57, SE-141 86 Stockholm, Sweden. Tel.: +46 8 58 58 6666; Fax: +46 8 58 58 5785; E-mail: markus.heilig{at}neurotec.ki.se

(Received 24 May 2004; first review notified 28 May 2004; in revised form 24 June 2004; accepted 29 June 2004)

Aims: To examine whether polymorphic variants of the HTR2C gene are associated with diagnosis of alcohol dependence. Methods: We compared allele frequencies of five HTR2C promoter polymorphisms in a Nordic population of alcohol dependent individuals (Males: n = 309; Females: n = 127) and ethnically matched controls (Males: n = 83; Females: n = 190) in whom alcohol dependence was established, or any diagnosis of substance disorder was excluded, respectively. Patients were further subtyped into Type I (late onset) and Type II (early onset) alcoholics. Results: None of the individual polymorphisms indicated significant association with alcohol dependence. A common promoter haplotype (GAGG) exhibited different distribution frequencies between males and females (Type I), however on Bonferroni's multiple-testing correction, this observation proved to be insignificant. Conclusions: Although we report a lack of association between alcohol dependence and five common promoter polymorphisms, and the constituted haplotypes, the analysis tends to indicate gender and sub-type differences. We suggest that a follow up study with larger sample numbers should be performed to improve the power to detect the genetic influences of HTR2C in alcohol dependence.


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