ROLE OF THE SEROTONIN TRANSPORTER PROMOTER POLYMORPHISM IN ANXIETY-RELATED TRAITS

Background: The heritability of interindividual variation in anxiety a nd other aspects of personality establishes that variants of genes inf luence these traits. A functional polymorphism in the promoter of the human serotonin transporter gene (SLC6A4C) was identified and found t o be linked to an anxiety-related personality trait, Neuroticism. The polymorphism affects gene transcription and, ultimately, gene function . We have attempted to confirm the role of SLC6A4C in anxiety-related personality traits by sibpair analysis and association studies. Metho ds: Sibpair linkage analysis and association study were performed in 6 55 Finns. The index cases were 182 alcoholic criminal offenders, throu gh which 255 relatives were ascertained to obtain 366 sibpairs. In add ition, 215 unrelated population controls were collected. Each individu al was psychiatrically interviewed, blind-rated for DSM-III-R diagnose s, and assessed with the Tridimensional Personality Questionnaire. Res ults: The sibpair analysis revealed a positive linkage between SLC6A4 C and the 2 anxiety-related subdimensions of Harm Avoidance: HA1 (Anti cipatory Worry) and HA2 (Fear of Uncertainty) (P=.003). How ever; ther e was no consistent association between SLC6A4C and any Tridimensiona l Personality Questionnaire trait. Conclusions: In the present study w e replicated the relationship of SLC6A4C to anxiety by sibpair linkag e analysis but found no evidence of association, raising the question of whether SLCM4''C locus is itself affecting anxiety or is linked to another still unknown functional variant.