Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: a systematic review and meta-analysis

被引:108
作者
Cho, HJ
Meira-Lima, I
Cordeiro, Q
Michelon, L
Sham, P
Vallada, H
Collier, DA
机构
[1] Univ London Kings Coll, Weston Educ Ctr, Inst Psychiat, Sect Gen hosp Psychiat, London SE5 9RJ, England
[2] Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil
关键词
bipolar disorder; serotonin transporter; polymorphisms; genetics; association study; meta; analysis;
D O I
10.1038/sj.mp.4001663
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The serotonin transporter (5-HTT) is a candidate gene for bipolar disorder (BPD). It has been investigated for association with the illness in a series of studies, but overall results have been inconsistent and its role in the disorder remains controversial. Systematic reviews using meta-analytical techniques are a useful method for objectively and reproducibly assessing individual studies and generating combined results. We performed two meta-analyses of published studies - both population-based and family-based studies - investigating the association between BPD and the 5-HTT gene-linked polymorphic region (5-HTTLPR) and the intron 2 variable numbers of tandem repeats ( VNTR) polymorphisms. The literature was searched using Medline and Embase to identify studies for inclusion. We statistically joined population-based and family-based studies into a single meta-analysis. For both polymorphisms, our review revealed significant pooled odds ratios (ORs): 1.12 (95% CI 1.03 - 1.21) for the 5-HTTLPR and 1.12 ( 95% CI 1.02 - 1.22) for the intron 2 VNTR. Meta-regression showed that neither the study type ( population-based vs family-based; P = 0.41 for the 5-HTTLPR and P = 0.91 for the intron 2 VNTR) nor the sample ethnicity ( Caucasian vs non-Caucasian; P = 0.35 for the 5-HTTLPR and P = 0.66 for the intron 2 VNTR) significantly contributed to the heterogeneity of the meta-analyses. The observed ORs could be regarded simply as a very small but detectable effect of the 5-HTT, which has an additive effect when combined with other susceptibility loci. Alternative hypotheses on this finding were also discussed: a stronger effect of the haplotypes involving the two polymorphisms or other SNP markers; a more direct effect of these polymorphisms on specific phenotypes of BPD; and the presence of gene - environment interaction as a mediator of the genetic effects of 5-HTT.
引用
收藏
页码:771 / 781
页数:11
相关论文
共 100 条
[81]   Catechol O-methyltransferase, serotonin transporter, and tryptophan hydroxylase gene polymorphisms in bipolar disorder patients with and without comorbid panic disorder [J].
Rotondo, A ;
Mazzanti, C ;
Dell'Osso, L ;
Rucci, P ;
Sullivan, P ;
Bouanani, S ;
Gonnelli, C ;
Goldman, D ;
Cassano, GB .
AMERICAN JOURNAL OF PSYCHIATRY, 2002, 159 (01) :23-29
[82]   Antidepressant-induced mania, rapid cycling and the serotonin transporter gene polymorphism [J].
Rousseva, A ;
Henry, C ;
van den Bulke, D ;
Fournier, G ;
Laplanche, JL ;
Leboyer, M ;
Bellivier, F ;
Aubry, JM ;
Baud, P ;
Boucherie, M ;
Buresi, C ;
Ferrero, F ;
Malafosse, A .
PHARMACOGENOMICS JOURNAL, 2003, 3 (02) :101-104
[83]  
Saleem Q, 2000, AM J MED GENET, V96, P170, DOI 10.1002/(SICI)1096-8628(20000403)96:2<170::AID-AJMG9>3.3.CO
[84]  
2-T
[85]   Genome scan meta-analysis of schizophrenia and bipolar disorder, part III:: Bipolar disorder [J].
Segurado, R ;
Detera-Wadleigh, SD ;
Levinson, DF ;
Lewis, CM ;
Gill, M ;
Nurnberg, JI ;
Craddock, N ;
DePaulo, JR ;
Baron, M ;
Gershon, ES ;
Ekholm, J ;
Cichon, S ;
Turecki, G ;
Claes, S ;
Kelsoe, JR ;
Schofield, PR ;
Badenhop, RF ;
Morissette, J ;
Coon, H ;
Blackwood, D ;
McInnes, LA ;
Foroud, T ;
Edenberg, HJ ;
Reich, T ;
Rice, JP ;
Goate, A ;
McInnis, MG ;
McMahon, FJ ;
Badner, JA ;
Goldin, LR ;
Bennett, P ;
Willour, VL ;
Zandi, PP ;
Liu, JJ ;
Gilliam, C ;
Juo, SH ;
Berrettini, WH ;
Yoshikawa, T ;
Peltonen, L ;
Lonnqvist, J ;
Nöthen, MM ;
Schumacher, J ;
Windemuth, C ;
Rietschel, M ;
Propping, P ;
Maier, W ;
Alda, M ;
Grof, P ;
Rouleau, GA ;
Del-Favero, J .
AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 73 (01) :49-62
[86]   Genetic features of antidepressant induced mania and hypo-mania in bipolar disorder [J].
Serretti, A ;
Artioli, P ;
Zanardi, R ;
Lorenzi, C ;
Rossini, D ;
Cusin, C ;
Arnoldi, A ;
Catalano, M .
PSYCHOPHARMACOLOGY, 2004, 174 (04) :504-511
[87]   Further evidence of a combined effect of SERTPR and TPH on SSRIs response in mood disorders [J].
Serretti, A ;
Cusin, C ;
Rossini, D ;
Artioli, P ;
Dotoli, D ;
Zanardi, R .
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2004, 129B (01) :36-40
[88]   Family-based association study of 5-HTTLPR, TPH, MAO-A, and DRD4 Polymorphisms in mood disorders [J].
Serretti, A ;
Cristina, S ;
Lilli, R ;
Cusin, C ;
Lattuada, E ;
Lorenzi, C ;
Corradi, B ;
Grieco, G ;
Costa, A ;
Santorelli, F ;
Barale, F ;
Nappi, G ;
Smeraldi, E .
AMERICAN JOURNAL OF MEDICAL GENETICS, 2002, 114 (04) :361-369
[89]   Serotonin transporter gene (5-HTTLPR) is not associated with depressive symptomatology in mood disorders [J].
Serretti, A ;
Cusin, C ;
Lattuada, E ;
DiBella, D ;
Catalano, M ;
Smeraldi, E .
MOLECULAR PSYCHIATRY, 1999, 4 (03) :280-283
[90]   Serotonin transporter gene not associated with psychotic symptomatology of mood disorders [J].
Serretti, A ;
Lattuada, E ;
Catalano, M ;
Smeraldi, E .
PSYCHIATRY RESEARCH, 1999, 86 (01) :59-65