Serotonin transporter gene and risk for bipolar affective disorder:: An association study in a Spanish population

Background: The serotonin transporter (5-HTT) is an important candidate gene for the genetic transmission of manic depressive illness. Many studies of patients with affective disorders have found abnormalities in serotonin metabolism and dysregulation of the transporter itself. In the present study, we hypothesize that genetic variation in the 5-HTT gene (17q11, 1-17q12) may have an effect in the etiology of manic depression. Methods: To test this hypothesis, we analyzed allele, genotype, and haplotype frequencies of two polymorphisms recently described in the 5-HTT gene (a variable number of tandem repeats in intron 2 and a deletion/insertion polymorphism in the transcriptional control region) in a sample of 88 patients with manic-depressive illness and 113 controls. Cases and controls were matched for ethnic and geographic origin. Results: No associations were found between any of these polymorphisms, rested individually or as haplotypes, and manic depression. Moreover, the genetic analysis by sex, presence/absence of psychiatric family history, and age of onset did not reveal significant differences in allele or genotype distributions. Conclusions: Our results suggest that the genetic variability of the 5-HTT gene is not a major risk factor for manic depression. (C) 1998 Society of Biological Psychiatry.