RGD Reference Report - Tryptophan hydroxylase-1 gene variants associate with a group of suicidal borderline women. - Rat Genome Database

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Tryptophan hydroxylase-1 gene variants associate with a group of suicidal borderline women.

Authors: Zaboli, G  Gizatullin, R  Nilsonne, A  Wilczek, A  Jonsson, EG  Ahnemark, E  Asberg, M  Leopardi, R 
Citation: Zaboli G, etal., Neuropsychopharmacology. 2006 Sep;31(9):1982-90. Epub 2006 Feb 22.
RGD ID: 5686357
Pubmed: PMID:16495936   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.npp.1301046   (Journal Full-text)

Alterations in the serotonin (5-HT) system have been related to impulsive aggression and suicidal behavior, common features of the borderline personality disorder (BPD). Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in 5-HT biosynthesis. Two isoforms are known, TPH-1 and TPH-2. TPH-1 has been correlated to various psychiatric and behavioral disorders by gene polymorphism association studies. We aimed to determine whether specific TPH-1 haplotypes associate with BPD. A case-control design was employed. The control group included 98 women without psychiatric history. In all, 95 patients were included, all Caucasian women with a BPD diagnosis who had attempted suicide at least twice during their lifetime. Exclusion criteria were: (i) substance dependence; (ii) dementia or other irreversible organic brain syndromes; (iii) psychotic disorders or major depressive illness with melancholic features; (iv) life-threatening eating disorders. Six single-nucleotide polymorphisms (SNPs) were found at significant linkage disequilibrium across 23 kb of the TPH-1 gene in both patients and controls, suggesting a haplotype block structure. While no individual SNP showed association, several haplotypes associated with the BPD group. In particular, one six-SNP haplotype was absent from the control group while representing about one-quarter of all haplotypes in the BPD group (corrected P<<10(-5)). A 'sliding window' analysis attributed the strongest disease association to haplotype configurations located between the gene promoter and intron 3. We conclude that TPH-1 associates with BPD in suicidal women. Our data support the expectation that haplotype analysis is superior to single locus analysis in gene-disease, case-control association studies.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
borderline personality disorder  IAGP 5686357DNA:SNPs and haplotypes: :multipleRGD 
borderline personality disorder  ISOTPH1 (Homo sapiens)5686357; 5686357DNA:SNPs and haplotypes: :multipleRGD 

Objects Annotated

Genes (Rattus norvegicus)
Tph1  (tryptophan hydroxylase 1)

Genes (Mus musculus)
Tph1  (tryptophan hydroxylase 1)

Genes (Homo sapiens)
TPH1  (tryptophan hydroxylase 1)


Additional Information