Antisocial alcoholism and serotonin-related polymorphisms: association tests.
Central serotonin dysfunction appears to be related to a subtype of alcoholism with antisocial impulsive features (type II; antisocial alcoholism). The serotonergic deficit may be associated with greater impulsivity, which in turn facilitates both alcohol dependence and antisocial behavior. The present study tested association of antisocial impulsive alcoholism with candidate genes related to serotonergic neurotransmission, using families. Eight markers were assayed using polymerase chain reaction: tryptophan hydroxylase (intron 7), the serotonin transporter SLC6A4 (VNTR 9/12), HTTLPR, the three serotonin receptor types HTR1B (G861C), HTR2A (T102C) and HTR2C (Cys23Ser), monoamine oxidase A (T1460C), and (CA)(n). Eligible probands had early age of onset of alcoholism, child conduct disorder, and two or more symptoms of adult Antisocial Personality Disorder. This sample included 35 probands, their parents, and some siblings (n = 116). Association tests were conducted using the Haplotype Relative Risk method for antisocial alcoholism diagnosis and the George-Elston regression method (the S.A.G.E. program ASSOC) for quantitative antisocial alcoholism severity. Haplotype Relative Risk analyses were not significant at the 0.05 level for any of the markers. Trends suggestive for future research occurred for tryptophan hydroxylase and HTR2A. Quantitative ASSOC analyses showed significant marker effects (P < 0.05) for both monoamine oxidase A markers, which were in linkage disequilibrium. Antisocial alcoholism symptom severity was higher with monoamine oxidase A C homozygotes or hemizygotes, indicating that low monoamine oxidase activity may be important. Future studies are needed to examine joint and interactive effects of serotonin-related markers.
Hill
Elizabeth M
EM
Department of Psychology, University of Detroit Mercy, Detroit, Michigan 48219, USA. hillelm@udmercy.edu
Stoltenberg
Scott F
SF
Bullard
Katherine Harris
KH
Li
Sheng
S
Zucker
Robert A
RA
Burmeister
Marget
M
D000328:Adult; D017668:Age of Onset; D000437:Alcoholism / Q000235:genetics* / Q000523:psychology*; D000483:Alleles; D000987:Antisocial Personality Disorder / Q000209:etiology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D003866:Depressive Disorder / Q000150:complications / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007438:Introns; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D018598:Minisatellite Repeats; D008995:Monoamine Oxidase / Q000235:genetics; D009419:Nerve Tissue Proteins; D009679:Nuclear Family; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011336:Probability; D020033:Protein Isoforms / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics; D012701:Serotonin / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins; D014365:Tryptophan Hydroxylase / Q000235:genetics
D002352:Carrier Proteins; D005819:Genetic Markers; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D011985:Receptors, Serotonin; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D014365:Tryptophan Hydroxylase; D008995:Monoamine Oxidase