Meta-analysis reveals association between serotonin transporter gene STin2 VNTR polymorphism and schizophrenia. 2005

J B Fan, and P Sklar
Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Massachusetts General Hospital, Charlestown, MA 02129, and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

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.

UI MeSH Term Description Entries
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D002874 Chromosome Mapping Any method used for determining the location of and relative distances between genes on a chromosome. Gene Mapping,Linkage Mapping,Genome Mapping,Chromosome Mappings,Gene Mappings,Genome Mappings,Linkage Mappings,Mapping, Chromosome,Mapping, Gene,Mapping, Genome,Mapping, Linkage,Mappings, Chromosome,Mappings, Gene,Mappings, Genome,Mappings, Linkage
D002886 Chromosomes, Human, Pair 17 A specific pair of GROUP E CHROMOSOMES of the human chromosome classification. Chromosome 17
D004251 DNA Transposable Elements Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom. DNA Insertion Elements,DNA Transposons,IS Elements,Insertion Sequence Elements,Tn Elements,Transposable Elements,Elements, Insertion Sequence,Sequence Elements, Insertion,DNA Insertion Element,DNA Transposable Element,DNA Transposon,Element, DNA Insertion,Element, DNA Transposable,Element, IS,Element, Insertion Sequence,Element, Tn,Element, Transposable,Elements, DNA Insertion,Elements, DNA Transposable,Elements, IS,Elements, Tn,Elements, Transposable,IS Element,Insertion Element, DNA,Insertion Elements, DNA,Insertion Sequence Element,Sequence Element, Insertion,Tn Element,Transposable Element,Transposable Element, DNA,Transposable Elements, DNA,Transposon, DNA,Transposons, DNA
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012559 Schizophrenia A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior. Dementia Praecox,Schizophrenic Disorders,Disorder, Schizophrenic,Disorders, Schizophrenic,Schizophrenias,Schizophrenic Disorder
D017384 Sequence Deletion Deletion of sequences of nucleic acids from the genetic material of an individual. Deletion Mutation,Deletion Mutations,Deletion, Sequence,Deletions, Sequence,Mutation, Deletion,Mutations, Deletion,Sequence Deletions
D050486 Serotonin Plasma Membrane Transport Proteins Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of serotonergic neurons. They are different than SEROTONIN RECEPTORS, which signal cellular responses to SEROTONIN. They remove SEROTONIN from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS. Regulates signal amplitude and duration at serotonergic synapses and is the site of action of the SELECTIVE SEROTONIN REUPTAKE INHIBITORS. Neurotransmitter Transport Proteins, Serotonin-Specific,Neurotransmitter Transporters, Serotonin-Specific,Serotonin Plasma Membrane Transporter Proteins,5-Hydroxytryptamine Plasma Membrane Transport Protein,5HT Transporter,Platelet Serotonin Transporter,SERT Proteins,SLC6A4 Protein,Serotonectin,Serotonin Transporter,Serotonin Transporter, Platelets,Sodium-Dependent Serotonin Transporter,Solute Carrier Family 6, Member 4 Protein,5 Hydroxytryptamine Plasma Membrane Transport Protein,Neurotransmitter Transport Proteins, Serotonin Specific,Neurotransmitter Transporters, Serotonin Specific,Platelets Serotonin Transporter,Serotonin Transporter, Platelet,Serotonin Transporter, Sodium-Dependent,Serotonin-Specific Neurotransmitter Transporters,Sodium Dependent Serotonin Transporter,Transporter, Sodium-Dependent Serotonin
D018598 Minisatellite Repeats Tandem arrays of moderately repetitive, short (10-60 bases) DNA sequences which are found dispersed throughout the GENOME, at the ends of chromosomes (TELOMERES), and clustered near telomeres. Their degree of repetition is two to several hundred at each locus. Loci number in the thousands but each locus shows a distinctive repeat unit. Minisatellite,Minisatellite Repeat,VNTR Loci,VNTR Region,VNTR Sequence,VNTR Sequences,Variable Number Of Tandem Repeat,Variable Number Tandem Repeat,Variable Number of Tandem Repeats,Variable Tandem Repeat,Minisatellites,Variable Number Tandem Repeats,Variable Tandem Repeats,Loci, VNTR,Locus, VNTR,Region, VNTR,Regions, VNTR,Repeat, Minisatellite,Repeat, Variable Tandem,Repeats, Minisatellite,Repeats, Variable Tandem,Sequence, VNTR,Sequences, VNTR,Tandem Repeat, Variable,Tandem Repeats, Variable,VNTR Locus,VNTR Regions

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