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 regio n of the human serotonin transporter (5-HTT) gene has been observed to be a ssociated 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. Si nce there is strong evidence of a disturbance in brain serotonergic transmi ssion among antisocial, impulsive, and violent type 2 alcoholic subjects, w e decided to test the hypothesis that the frequency of the S allele, which is associated with reduced 5-HTT gene expression, is higher among habituall y violent type 2 alcoholics when compared with race and gender-matched heal thy controls and non-violent late-onset (type 1) alcoholics, The 5-HTT prom oter 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 subjec ts and controls were white Caucasian males of Finnish origin. The S allele frequency was higher among type 2 alcoholics compared with type 1 alcoholic s chi(2)=4.86, P=0.028 and healthy controls chi(2) = 8.24, P = 0.004, The o dds ratio for SS genotype vs LL genotype was 3.90, 95% CI 1.37-11.11, P=0.0 11 when type 2 alcoholics were compared with healthy controls. The results suggest that the 5-HTT 'S' promoter polymorphism is associated with an incr eased risk for early onset alcoholism associated with antisocial personalit y disorder and impulsive, habitually violent behavior.