ASSOCIATION STUDIES OF BIPOLAR DISORDER AT THE HUMAN SEROTONIN TRANSPORTER GENE (HSERT, 5HTT)

The human serotonin transporter gene (hSERT) is a strong candidate for involvement in the pathogenesis of mood disorder and, using a UK Cauc asian case-control sample, Collier ef al found a significant associati on between bipolar disorder and the 12 allele of the VNTR polymorphism in intron 2 of this gene. In a European collaborative sample, Collier et al found a significant association between affective disorder and a functional deletion polymorphism in the promoter of hSERT. We have u ndertaken association studies using these polymorphisms in a British C aucasian sample comprising 171 DSM-IV bipolar probands, 80 DSM-IV majo r depression probands and 121 unrelated controls matched to bipolar pr obands for age, sex and ethnicity. We found no association between the promoter deletion and affective disorder but our findings with the VN TR polymorphism are similar to those of Collier and colleagues: we fou nd a significant excess of the 12 repeat allele in bipolar probands (P = 0.031, one-tail) with a suggestion of a gene dosage effect (using ge notypes bearing no 12 repeat allele as baseline, the increased risks c onferred by genotypes bearing 12 repeat alleles were: heterozygote, OR = 1.24; homozygote, OR = 1.76). Our findings add to the evidence that variation at or near hSERT influences susceptibility to bipolar disor der in the British Caucasian population.