Abstract
The serotonin transporter (5-HTT) is a candidate locus for aetiological involvement in affective disorders. Biochemical studies in suicides and depressed patients suggest that 5-HT uptake function is frequently reduced in affective illness. Furthermore, 5-HTT is targeted by widely used antidepressant drugs such as fluoxetine. We have performed an association study of a short variant of the 5-HTT-linked polymorphic region (5-HTTLPR), which restricts transcriptional activity of the 5-HTT promoter leading to low functional expression of the 5-HTT, in 454 patients with bipolar or unipolar affective disorder and 570 controls, derived from three European Centres (London, Milan and Würzburg). In all three centres, the frequency of the low activity allele was higher in patients than in controls (50% vs 45% in London, 45% vs 43% in Milan, 47% vs 40% in Würzburg). Although these differences were not individually significant, a stratified analysis of all three samples gave a significant overall odds ratio of 1.23 (95% confidence interval 1.02-1.49, P = 0.03). The excess of the homozygous low-activity genotype among the patients was even greater (odds ratio 1.53, 95% confidence interval 1.04-2.23, P = 0.02), suggesting partial recessivity of the low-activity allele. Given the functional role of 5-HTT, our findings suggest that 5-HTTLPR-dependent variation in functional 5-HTT expression is a potential genetic susceptibility factor for affective disorders. If this finding is replicated, further work on genetic variants with low 5-HTT activity may facilitate the differential diagnosis of affective disorders, the assessment of suicidal behaviour, and the prediction of good clinical response to antidepressants.
| Original language | English |
|---|---|
| Pages (from-to) | 453-460 |
| Number of pages | 8 |
| Journal | Molecular Psychiatry |
| Volume | 1 |
| Issue number | 6 |
| Publication status | Published - 1996 |
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Keywords
- Association
- Bipolar disorder
- Case-control
- Depression
- Genetics
- QTL
- Serotonin transporter
ASJC Scopus subject areas
- Molecular Biology
- Psychiatry and Mental health
Cite this
A novel functional polymorphism within the promoter of the serotonin transporter gene : Possible role in susceptibility to affective disorders. / Collier, D. A.; Stöber, G.; Li, T.; Heils, A.; Catalano, M.; Di Bella, D.; Arranz, M. J.; Murray, R. M.; Vallada, H. P.; Bengel, D.; Müller, C. R.; Roberts, G. W.; Smeraldi, E.; Kirov, G.; Sham, P.; Lesch, K. P.
In: Molecular Psychiatry, Vol. 1, No. 6, 1996, p. 453-460.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A novel functional polymorphism within the promoter of the serotonin transporter gene
T2 - Possible role in susceptibility to affective disorders
AU - Collier, D. A.
AU - Stöber, G.
AU - Li, T.
AU - Heils, A.
AU - Catalano, M.
AU - Di Bella, D.
AU - Arranz, M. J.
AU - Murray, R. M.
AU - Vallada, H. P.
AU - Bengel, D.
AU - Müller, C. R.
AU - Roberts, G. W.
AU - Smeraldi, E.
AU - Kirov, G.
AU - Sham, P.
AU - Lesch, K. P.
PY - 1996
Y1 - 1996
N2 - The serotonin transporter (5-HTT) is a candidate locus for aetiological involvement in affective disorders. Biochemical studies in suicides and depressed patients suggest that 5-HT uptake function is frequently reduced in affective illness. Furthermore, 5-HTT is targeted by widely used antidepressant drugs such as fluoxetine. We have performed an association study of a short variant of the 5-HTT-linked polymorphic region (5-HTTLPR), which restricts transcriptional activity of the 5-HTT promoter leading to low functional expression of the 5-HTT, in 454 patients with bipolar or unipolar affective disorder and 570 controls, derived from three European Centres (London, Milan and Würzburg). In all three centres, the frequency of the low activity allele was higher in patients than in controls (50% vs 45% in London, 45% vs 43% in Milan, 47% vs 40% in Würzburg). Although these differences were not individually significant, a stratified analysis of all three samples gave a significant overall odds ratio of 1.23 (95% confidence interval 1.02-1.49, P = 0.03). The excess of the homozygous low-activity genotype among the patients was even greater (odds ratio 1.53, 95% confidence interval 1.04-2.23, P = 0.02), suggesting partial recessivity of the low-activity allele. Given the functional role of 5-HTT, our findings suggest that 5-HTTLPR-dependent variation in functional 5-HTT expression is a potential genetic susceptibility factor for affective disorders. If this finding is replicated, further work on genetic variants with low 5-HTT activity may facilitate the differential diagnosis of affective disorders, the assessment of suicidal behaviour, and the prediction of good clinical response to antidepressants.
AB - The serotonin transporter (5-HTT) is a candidate locus for aetiological involvement in affective disorders. Biochemical studies in suicides and depressed patients suggest that 5-HT uptake function is frequently reduced in affective illness. Furthermore, 5-HTT is targeted by widely used antidepressant drugs such as fluoxetine. We have performed an association study of a short variant of the 5-HTT-linked polymorphic region (5-HTTLPR), which restricts transcriptional activity of the 5-HTT promoter leading to low functional expression of the 5-HTT, in 454 patients with bipolar or unipolar affective disorder and 570 controls, derived from three European Centres (London, Milan and Würzburg). In all three centres, the frequency of the low activity allele was higher in patients than in controls (50% vs 45% in London, 45% vs 43% in Milan, 47% vs 40% in Würzburg). Although these differences were not individually significant, a stratified analysis of all three samples gave a significant overall odds ratio of 1.23 (95% confidence interval 1.02-1.49, P = 0.03). The excess of the homozygous low-activity genotype among the patients was even greater (odds ratio 1.53, 95% confidence interval 1.04-2.23, P = 0.02), suggesting partial recessivity of the low-activity allele. Given the functional role of 5-HTT, our findings suggest that 5-HTTLPR-dependent variation in functional 5-HTT expression is a potential genetic susceptibility factor for affective disorders. If this finding is replicated, further work on genetic variants with low 5-HTT activity may facilitate the differential diagnosis of affective disorders, the assessment of suicidal behaviour, and the prediction of good clinical response to antidepressants.
KW - Association
KW - Bipolar disorder
KW - Case-control
KW - Depression
KW - Genetics
KW - QTL
KW - Serotonin transporter
UR - http://www.scopus.com/inward/record.url?scp=0030320649&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030320649&partnerID=8YFLogxK
M3 - Article
VL - 1
SP - 453
EP - 460
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
IS - 6
ER -