Structure of a variable number tandem repeat of the serotonin transporter gene and association with affective disorder.

We have recently reported an association between a polymorphism of a variable number tandem repeat (VNTR) region of the serotonin transporter gene and susceptibility to major depressive disorder. We identified three alleles containing respectively 9 (STin2.9), 10 (STin2.10) and 12 (STin2.12) copies of a repetitive element. We report here the sequences of the three alleles. The repetitive element conformed to the consensus sequence, GGCTGYGACCY(R)GRRTG, where Y = T/C, R = G/A, with loss of the 12th base pair in one of the repeating elements. We have also extended the numbers of cases and controls in the study. The frequencies of the three alleles in 119 individuals with single or recurrent major depressive episodes, 128 individuals with bipolar disorder and a group of 346 controls were compared. There was a significant difference between patients with affective disorder and controls in the proportion of individuals carrying the STin2.9 allele. For the risk of unipolar disorder given a single STin2.9 allele, the odds ratio was 4.44 (95% Cl, 1.65-11.95) and for bipolar disorder 3.22 (95% Cl, 1.15-9.09). The findings support the hypothesis that allelic variation in the serotonin transporter gene may contribute to susceptibility for both major depression and bipolar disorder.