Association between low activity serotonin transporter promoter genotype and early onset alcoholism with habitual impulsive violent behavior

T Hallikainen, T Saito, HM Lachman, J Volavka… - Molecular …, 1999 - nature.com
T Hallikainen, T Saito, HM Lachman, J Volavka, T Pohjalainen, OP Ryynänen, J Kauhanen
Molecular psychiatry, 1999nature.com
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 …
Abstract
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 (χ 2= 4.86, P= 0.028) and healthy controls (χ 2= 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.
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