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
[31]   An intronic polymorphic domain often associated with susceptibility to affective disorders has allele dependent differential enhancer activity in embryonic stem cells [J].
Fiskerstrand, CE ;
Lovejoy, EA ;
Quinn, JP .
FEBS LETTERS, 1999, 458 (02) :171-174
[32]  
Furlong RA, 1998, AM J MED GENET, V81, P58, DOI 10.1002/(SICI)1096-8628(19980207)81:1<58::AID-AJMG11>3.0.CO
[33]  
2-V
[34]  
Gelernter J, 1999, AM J MED GENET, V88, P61, DOI 10.1002/(SICI)1096-8628(19990205)88:1<61::AID-AJMG11>3.0.CO
[35]  
2-K
[36]   Antidepressant-induced mania: an overview of current controversies [J].
Goldberg, JF ;
Truman, CJ .
BIPOLAR DISORDERS, 2003, 5 (06) :407-420
[37]   Serotonin transporter gene and risk for bipolar affective disorder:: An association study in a Spanish population [J].
Gutiérrez, B ;
Arranz, MJ ;
Collier, DA ;
Vallès, V ;
Guillamat, R ;
Bertranpetit, J ;
Murray, RM ;
Fañanás, L .
BIOLOGICAL PSYCHIATRY, 1998, 43 (11) :843-847
[38]   Association analysis of the insertion/deletion polymorphism in serotonin transporter gene in patients with affective disorder [J].
Hauser, J ;
Leszczynska, A ;
Samochowiec, J ;
Czerski, PM ;
Ostapowicz, A ;
Chlopocka, M ;
Horodnicki, J ;
Rybakowski, JK .
EUROPEAN PSYCHIATRY, 2003, 18 (03) :129-132
[39]   Association studies of candidate genes in bipolar disorders [J].
Heiden, A ;
Schüssler, P ;
Itzlinger, U ;
Leisch, F ;
Scharfetter, J ;
Gebhardt, C ;
Fuchs, K ;
Willett, M ;
Nilsson, L ;
Miller-Reiter, E ;
Stompe, T ;
Meszaros, K ;
Sieghart, W ;
Hornik, K ;
Kasper, S ;
Aschauer, HN .
NEUROPSYCHOBIOLOGY, 2000, 42 :18-21
[40]  
Ho LW, 2000, AM J MED GENET, V96, P36