Serotonin transporter gene polymorphisms: ethnic difference and possible association with bipolar affective disorder

Mol Psychiatry. 1997 Oct-Nov;2(6):457-62. doi: 10.1038/


There is some evidence suggesting that a polymorphism of variable number of tandem repeats (VNTR) in the second intron of the serotonin transporter (5-HTT) gene and another variation which lies 1.2 kb upstream of the promoter of the gene (5-HTTLPR) are associated with affective disorders. However, conflicting results have also been reported. We examined an allelic association of these two polymorphisms in a Japanese sample of 191 patients with affective disorders (142 bipolar and 49 unipolar) and 212 controls. Substantial differences in the number and frequency of alleles between Caucasians and Japanese were observed for both polymorphisms. A significant association between the VNTR polymorphism 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 found, 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 relatively small number of subjects with unipolar depression. Our results suggest 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Asian People / genetics*
  • Base Sequence
  • Bipolar Disorder / genetics*
  • Carrier Proteins / genetics*
  • DNA Transposable Elements
  • Depressive Disorder / genetics*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Japan
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins*
  • Middle Aged
  • Molecular Sequence Data
  • Nerve Tissue Proteins*
  • Polymorphism, Genetic*
  • Reference Values
  • Repetitive Sequences, Nucleic Acid*
  • Serotonin / metabolism
  • Serotonin Plasma Membrane Transport Proteins
  • White People / genetics*


  • Carrier Proteins
  • DNA Transposable Elements
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin