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

• DOI: 10.1038/sj.mp.4000526
• Publication Date: 2002-09-04T18:44:31Z
• Authors: T Hallikainen; T Saito; H M Lachman; J Volavka; T Pohjalainen; O-P Ryynänen; J Kauhanen; E Syvälahti; J Hietala; J Tiihonen
• Keywords: Adult; Male; Serotonin Plasma Membrane Transport Proteins; Membrane Glycoproteins; Genotype; Membrane Transport Proteins; Nerve Tissue Proteins; Violence; White People; Alcoholism; 03 medical and health sciences; 0302 clinical medicine; Gene Expression Regulation; Reference Values; Impulsive Behavior; Humans; Age of Onset; Carrier Proteins; Promoter Regions, Genetic; Alleles; Finland

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.