The serotonin transporter is a potential susceptibility factor for bipolar affective disorder.
The serotonin transporter is a strong candidate for aetiological involvement in affective disorders and psychosis. We analysed a VNTR in intron 2 of the human serotonin transporter gene (hSERT) for allelic association with bipolar affective disorder, unipolar depression and schizophrenia. An increased frequency of allele 12 of the VNTR was observed in subjects with bipolar affective disorder (n = 191; chi 2 p = 0.00048 by allele) but not unipolar depression (n = 86; chi 2 p = 0.18, ns) or schizophrenia (n = 129; chi 2 p = 0.08, ns), although a trend towards an excess of allele 12 was observed for the latter. There was also a significant difference in the frequency of allele 12 between bipolar affective disorder and unipolar depression (p = 0.0087). The relative risk for bipolar affective disorder with respect to allele 12 was 1.84 (95% CI 0.97-3.56) for heterozygotes, and 3.10 (95% CI 1.60-6.07) for homozygotes, with evidence for a gene-dosage effect. Because allele 12 is common in the population, the attributable risk is 50.8% (95% CI 14.5%-73.3%). We hypothesize that either the VNTR affects regulation of expression of hSERT at the transcriptional level or it is in linkage disequilibrium with another functional polymorphism in the gene, and this results in an increased risk for the development of bipolar affective disorder.
Department of Psychological Medicine, Institute of Psychiatry, London, UK.
D A
DA
Collier
M J
MJ
Arranz
P
P
Sham
S
S
Battersby
H
H
Vallada
P
P
Gill
K J
KJ
Aitchison
M
M
Sodhi
T
T
Li
G W
GW
Roberts
B
B
Smith
J
J
Morton
R M
RM
Murray
D
D
Smith
G
G
Kirov
D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D018598:Minisatellite Repeats; D009419:Nerve Tissue Proteins; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins