Association between low activity serotonin transporter promoter genotype and early onset alcoholism with habitual impulsive violent behavior.
A common 44-base pair insertion/deletion polymorphism in the promoter region of the human serotonin transporter (5-HTT) gene has been observed to be associated with affective illness and anxiety-related traits. This biallelic functional polymorphism, designated long (L) and short (S), affects 5-HTT gene expression since the S promoter is less active than the L promoter. Since there is strong evidence of a disturbance in brain serotonergic transmission among antisocial, impulsive, and violent type 2 alcoholic subjects, we decided to test the hypothesis that the frequency of the S allele, which is associated with reduced 5-HTT gene expression, is higher among habitually violent type 2 alcoholics when compared with race and gender-matched healthy controls and non-violent late-onset (type 1) alcoholics. The 5-HTT promoter genotype was determined by a PCR-based method in 114 late onset (type 1) non-violent alcoholics, 51 impulsive violent recidivistic offenders with early onset alcoholism (type 2), and 54 healthy controls. All index subjects and controls were white Caucasian males of Finnish origin. The S allele frequency was higher among type 2 alcoholics compared with type 1 alcoholics (chi2 = 4.86, P = 0.028) and healthy controls (chi2 = 8.24, P = 0.004). The odds ratio for SS genotype vs LL genotype was 3.90, 95% Cl 1.37-11.11, P = 0.011 when type 2 alcoholics were compared with healthy controls. The results suggest that the 5-HTT 'S' promoter polymorphism is associated with an increased risk for early onset alcoholism associated with antisocial personality disorder and impulsive, habitually violent behavior.
Hallikainen
T
T
Department of Forensic Psychiatry, University of Kuopio, Niuvanniemi Hospital, 70240 Kuopio, Finland.
Saito
T
T
Lachman
H M
HM
Volavka
J
J
Pohjalainen
T
T
Ryynänen
O P
OP
Kauhanen
J
J
Syvälahti
E
E
Hietala
J
J
Tiihonen
J
J
D000328:Adult; D017668:Age of Onset; D000437:Alcoholism / Q000235:genetics* / Q000523:psychology*; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D005387:Finland; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D007175:Impulsive Behavior / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011401:Promoter Regions, Genetic; D012016:Reference Values; D050486:Serotonin Plasma Membrane Transport Proteins; D014754:Violence; D044465:White People / Q000235:genetics*
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins