Polymorphism in serotonin transporter gene associated with susceptibility to major depression.
BACKGROUND; The serotonin transporter of the brain provides the primary target for the action of selective antidepressant drugs. We set out to identify polymorphisms of the serotonin transporter gene and to find out whether there was a relation between any such polymorphisms and the occurrence of affective disorder.


METHODS
A comparison of a polymorphic region of the human serotonin transporter gene was carried out between two groups. The study group comprised 83 patients (39 unipolar depressive disorder, 44 bipolar disorder) with major affective disorder. The control group comprised 122 anonymous blood donors, and 71 volunteers who had been screened for psychiatric disorders.


RESULTS
We detected three novel alleles of the variable-number-tandem-repeat (VNTR) region (STin2.9, STin2.10) and Stin2.12) containing nine, ten and 12 copies of the VNTR element, respectively. The frequencies of the different forms of the allele in the control group were compared with those in the affective disorder group. There was a significant difference between the control and affective disorder groups, largely explained by the excess of the STin2.9 allele in the unipolar group (chi2=10.05, p<0.004 [Bonferroni corrected]). The presence of the allele with nine copies of the repeat was significantly associated with risk of unipolar disorder (odds ratio=6.95 [95% CI 1.8-27.2]).


CONCLUSIONS
This association, for an obvious candidate gene, may provide a critical starting point for an understanding of the likely polygenic contributions towards susceptibility to affective disorder.
Ogilvie
A D
AD
Medical Research Council, Brain Metabolism Unit, Royal Edinburgh Hospital,Edinburgh, UK.
Battersby
S
S
Bubb
V J
VJ
Fink
G
G
Harmar
A J
AJ
Goodwim
G M
GM
Smith
C A
CA
D000483:Alleles; D001483:Base Sequence; D001714:Bipolar Disorder / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D017931:DNA Primers; D003866:Depressive Disorder / Q000235:genetics*; D004198:Disease Susceptibility; D005787:Gene Frequency; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012701:Serotonin / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D017931:DNA Primers; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin