MUTATION SCREENING OF THE 5-HYDROXYTRYPTAMINE(7) RECEPTOR GENE AMONG FINNISH ALCOHOLICS AND CONTROLS

Impaired central serotonin neurotransmission has been associated with increased aggression, impaired impulse control and diurnal activity rh ythm disturbances among humans. Neuroanatomic distribution and pharmac ological properties of the serotonin 5-HT7 receptor suggest that it ma y play a role in psychiatric disorders and in circadian rhythm regulat ion. In this study a point mutation causing proline(279) --> leucine a mino acid substitution in the 5-hydroxytryptamine(7) (5-HT7) receptor gene was discovered. This 5-HT7Leu279 variant was observed in six of 8 25 individuals, all of whom are heterozygous for the substitution. Thr ee of them are alcoholic offenders (3/255), two are relatives of an of fender without the 5-HT7Leu279 allele (2/255) and one is a healthy con trol without any psychiatric diagnosis (1/248). The allele frequency o f the 5-HT7Leu279 variant is 0.004 (6/758) among Finns. Although the 5 -HT7Leu279 variant is approximately three times more common among alco holic offenders than among healthy controls, it is not significantly a ssociated with alcoholism or impulsivity in the present study. The 5-H T7Leu279 allele may, however, be a predisposing allele in a subgroup o f alcoholic offenders with multiple behavioral problems. (C) 1998 Else vier Science Ireland Ltd.