Association of DNA Polymorphisms in the synaptic vesicular amine transporter gene (SLCI8A2) with alcohol and nicotine dependence

被引:33
作者
Schwab, SG
Franke, PE
Hoefgen, B
Guttenthaler, V
Lichtermann, D
Trixler, M
Knapp, M
Maier, W
Wildenauer, DB
机构
[1] Sir Charles Gairdner Hosp, Western Australian Inst Med Res, Nedlands, WA 6009, Australia
[2] Univ Western Australia, Sch Psychiat & Clin Neurosci, Perth, WA 6009, Australia
[3] Univ Western Australia, Med Res Ctr, Perth, WA 6009, Australia
[4] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany
[5] Methadon Maintenance Clin Cafe Ersatz, Bonn, Germany
[6] Univ Pecs, Dept Psychiat, Pecs, Hungary
[7] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-5300 Bonn, Germany
[8] Univ Western Australia, Ctr Clin Res Neuropsychiat, Mt Claremont, WA, Australia
关键词
synaptic vesicular amine transporter; alcohol dependence; nicotine dependence; association; transmission disequilibrium test; substance dependence;
D O I
10.1038/sj.npp.1300809
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The brain synaptic vesicular amine transporter SLCA18A2 is a key component for the uptake of monoamines like dopamine or serotonin into vesicles. We have analyzed seven DNA polymorphisms located in the genomic region of SLC18A2 for association with alcohol- and nicotine dependence, using a family-based design. Our sample comprised 131 families with alcohol- dependent offspring and 96 families with at least one nicotine-dependent offspring. For the alcohol- dependent sample, we found statistical significant association for two single markers (rs363387, P = 0.03; rs363333, P = 0.0066) as well as for several haplotypes ( minimal P = 0.0038). When the sample with alcohol dependence was stratified according to gender, we observed increased association for the male subgroup ( rs363387, P = 0.0011). None of the markers showed association in the sample of families with nicotine dependence. However, analysis of a combined sample of alcohol and nicotine-dependent families resulted in single markers as well as several haplotypes showing statistical significant association with substance dependence ( minimal P = 0.0044). We conclude that DNA polymorphisms located in SLC18A2 might contribute to the development of substance dependence.
引用
收藏
页码:2263 / 2268
页数:6
相关论文
共 24 条
[1]   A powerful strategy to account for multiple testing in the context of haplotype analysis [J].
Becker, T ;
Knapp, M .
AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 75 (04) :561-570
[2]   Maximum-likelihood estimation of haplotype frequencies in nuclear families [J].
Becker, T ;
Knapp, M .
GENETIC EPIDEMIOLOGY, 2004, 27 (01) :21-32
[3]   A genomic scan for habitual smoking in families of alcoholics: Common and specific genetic factors in substance dependence [J].
Bierut, LJ ;
Rice, JP ;
Goate, A ;
Hinrichs, AL ;
Saccone, NL ;
Foroud, T ;
Edenberg, HJ ;
Cloninger, CR ;
Begleiter, H ;
Conneally, PM ;
Crowe, RR ;
Hesselbrock, V ;
Li, TK ;
Nurnberger, JI ;
Porjesz, B ;
Schuckit, MA ;
Reich, T .
AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2004, 124A (01) :19-27
[4]  
CLONINGER C R, 1988, Advances in Alcohol and Substance Abuse, V7, P3
[5]  
Dinwiddie Stephen H., 1993, Journal of Addictive Diseases, V12, P17, DOI 10.1300/J069v12n03_03
[6]   DAT1 gene polymorphism in alcoholism:: A family-based association study [J].
Franke, P ;
Schwab, SG ;
Knapp, M ;
Gänsicke, M ;
Delmo, C ;
Zill, P ;
Trixler, M ;
Lichtermann, D ;
Hallmayer, J ;
Wildenauer, DB ;
Maier, W .
BIOLOGICAL PSYCHIATRY, 1999, 45 (05) :652-654
[7]   Sex-dependent modulation of ethanol consumption in vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) knockout mice [J].
Hall, FS ;
Sora, I ;
Uhl, GR .
NEUROPSYCHOPHARMACOLOGY, 2003, 28 (04) :620-628
[8]  
HEATHERTON TF, 1991, BRIT J ADDICT, V86, P1119
[9]   Correlation between dopamine D2 receptors in the ventral striatum and central processing of alcohol cues and craving [J].
Heinz, A ;
Siessmeier, T ;
Wrase, J ;
Hermann, D ;
Klein, S ;
Grüsser-Sinopoli, SM ;
Flor, H ;
Braus, DF ;
Buchholz, HG ;
Gründer, G ;
Schreckenberger, M ;
Smolka, MN ;
Rösch, F ;
Mann, K ;
Bartenstein, P .
AMERICAN JOURNAL OF PSYCHIATRY, 2004, 161 (10) :1783-1789
[10]  
HENRY JP, 1994, J EXP BIOL, V196, P251