SEROTONIN TRANSPORTER GENE POLYMORPHISMS - ETHNIC DIFFERENCE AND POSSIBLE ASSOCIATION WITH BIPOLAR AFFECTIVE-DISORDER

There is some evidence suggesting that a polymorphism of variable numb er of tandem repeats (VNTR) in the second intron of the serotonin tran sporter (5-HTT) gene and another variation which lies 1.2 kb upstream of the promoter of the gene (5-HTTLPR) are associated with affective d isorders. However, conflicting results have also been reported. We exa mined an allelic association of these two polymorphisms in a Japanese sample of 191 patients with affective disorders (142 bipolar and 49 un ipolar) and 212 controls. Substantial differences in the number and fr equency of alleles between Caucasians and Japanese were observed for b oth polymorphisms. A significant association between the VNTR polymorp hism and bipolar disorder (genotypic association: odds ratio 2.2, 95% CI 1.2-4.0; allelic association: odds ratio 1.7, 95% CI 1.0-3.0) was f ound, but not between the 5-HTTLPR polymorphism and bipolar disorder. No significant association with unipolar depression was detected using either genetic marker, although this may be attributable to the relat ively small number of subjects with unipolar depression. Our results s uggest that the VNTR itself or another unknown functional polymorphism which would be in linkage disequilibrium to the VNTR has an effect on susceptibility to bipolar disorder.