A TRYPTOPHAN-HYDROXYLASE GENE MARKER FOR SUICIDALITY AND ALCOHOLISM

Background: Tryptophan hydroxylase (TPH) is the rate-limiting enzyme i n the synthesis of serotonin. Low turnover rate of this monoamine neur otransmitter is associated with impaired impulse control. We previousl y reported that, in Finns, TPH genotype was associated with suicidalit y, a pathophysiological mechanism that may involve impaired impulse co ntrol. Methods: Association and sib-pair linkage analyses of a polymor phism in intron 7 of the TPH gene with suicidality, alcoholism, and th e Karolinska Scales of Personality were conducted in 804 Finnish alcoh olic offenders, controls, and their relatives, in a sample that includ ed 369 sib pairs. Results: The association of the TPH 17 779C (L) alle le to suicidality in impulsive offenders reported previously was repli cated in a new group of Finnish offenders (P=.001, n=122). The intron 7 variant in the TPH gene showed significant evidence for linkage to s uicidality (P=.006 in unaffected sib pairs), severe suicide attempts ( P=.006 in unaffected sib pairs; regression: P=.01), alcoholism (P=.003 in unaffected sib-pairs; regression: P=.02), and Karolinska Scales of Personality socialization score (regression: P=.002). Conclusions: Th e status of the TPH A779C allele as a marker for suicidality was repli cated and linkage with alcoholism and Karolinska Scales of Personality socialization score was also observed. A functional variant(s) in or close to the TPH gene may predispose individuals to suicidality and ot her behaviors thought to be influenced by serotonin.