Meta-analysis reveals association between serotonin transporter gene STin2 VNTR polymorphism and schizophrenia

被引:111
作者
Fan, JB
Sklar, P
机构
[1] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Charlestown, MA 02129 USA
[2] MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA
[3] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA
关键词
schizophrenia; meta-analysis; SLC6A4; 5-HTTLPR; STin2; VNTR;
D O I
10.1038/sj.mp.4001690
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 gene (SLC6A4) is a candidate gene for schizophrenia based on serotonin transporter's crucial role in serotonergic neurotransmission. However, association studies have produced conflicting results regarding the association between two common SLC6A4 gene polymorphisms, the promoter insertion/ deletion (5-HTTLPR) and the intron 2 VNTR (STin2 VNTR) polymorphisms, and schizophrenia susceptibility. To further elucidate the putative association between the two SLC6A4 gene polymorphisms and schizophrenia susceptibility, we performed a meta-analysis based on all original published association studies between schizophrenia and the 5-HTTLPR and STin2 VNTR polymorphisms published before April 2004. Our analyses showed no statistically significant evidence for the association between the Short allele of the 5-HTTLPR polymorphism and schizophrenia ( random-effects pooled odds ratio ( OR) 0.99, 95% Confidence Interval ( CI) 0.92 - 1.07, Z = - 0.23, P = 0.82) from 19 population-based association studies consisting of 2990 case and 3875 control subjects. However, highly significant evidence for association between the STin2.12 allele of the STin2 VNTR polymorphism ( random-effects pooled OR 1.24, 95% CI 1.11 - 1.38, Z = 3.82, P = 0.00014) and schizophrenia was found from 12 population-based association studies consisting of 2177 cases and 2369 control subjects. Our meta-analysis suggests that the STin2.12 allele of the STin2 VNTR polymorphism is likely a risk factor for schizophrenia susceptibility. Our data imply that following completion of the International HapMap Project, a comprehensive evaluation of a set of markers that fully characterize the linkage disequilibrium relationships at the SLC6A4 gene should be tested in large well-characterized clinical samples in order to understand the role of this gene in schizophrenia susceptibility.
引用
收藏
页码:928 / 938
页数:11
相关论文
共 90 条
[1]   Meta-analysis of association between the T102C polymorphism of the 5HT2a receptor gene and schizophrenia [J].
Abdolmaleky, HM ;
Faraone, SV ;
Glatt, SJ ;
Tsuang, MT .
SCHIZOPHRENIA RESEARCH, 2004, 67 (01) :53-62
[2]   Guilt by association [J].
Altshuler, D ;
Daly, M ;
Kruglyak, L .
NATURE GENETICS, 2000, 26 (02) :135-137
[3]   A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: I. Affective disorders [J].
Anguelova, M ;
Benkelfat, C ;
Turecki, G .
MOLECULAR PSYCHIATRY, 2003, 8 (06) :574-591
[4]   A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: II. Suicidal behavior [J].
Anguelova, M ;
Benkelfat, C ;
Turecki, G .
MOLECULAR PSYCHIATRY, 2003, 8 (07) :646-653
[5]   Testing for population subdivision and association in four case-control studies [J].
Ardlie, KG ;
Lunetta, KL ;
Seielstad, M .
AMERICAN JOURNAL OF HUMAN GENETICS, 2002, 71 (02) :304-311
[6]   The serotonin transporter and clozapine response [J].
Arranz, MJ ;
Bolonna, AA ;
Munro, J ;
Curtis, CJ ;
Collier, DA ;
Kerwin, RW .
MOLECULAR PSYCHIATRY, 2000, 5 (02) :124-125
[7]   Haploview: analysis and visualization of LD and haplotype maps [J].
Barrett, JC ;
Fry, B ;
Maller, J ;
Daly, MJ .
BIOINFORMATICS, 2005, 21 (02) :263-265
[8]   5HTTLPR polymorphism in schizophrenic patients:: Further support for association with violent suicide attempts [J].
Bayle, FJ ;
Leroy, S ;
Gourion, D ;
Millet, B ;
Olié, JP ;
Poirier, MF ;
Krebs, MO .
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2003, 119B (01) :13-17
[9]   Serotonin transporter gene polymorphism and schizophrenia: An association study [J].
BonnetBrilhault, F ;
Laurent, C ;
Thibaut, F ;
Campion, D ;
Chavand, O ;
Samolyk, D ;
Martinez, M ;
Petit, M ;
Mallet, J .
BIOLOGICAL PSYCHIATRY, 1997, 42 (07) :634-636
[10]   Large trials vs meta-analysis of smaller trials - How do their results compare? [J].
Cappelleri, JC ;
Ioannidis, JPA ;
Schmid, CH ;
deFerranti, SD ;
Aubert, M ;
Chalmers, TC ;
Lau, J .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1996, 276 (16) :1332-1338