title: Interaction between tryptophan hydroxylase I polymorphisms and childhood abuse is associated with increased risk for borderline personality disorder in adulthood.
abstract: BACKGROUND
  Borderline personality disorder (BPD) is a severe disorder with high morbidity and mortality, but unknown etiology. Childhood abuse has been proposed as an etiological factor, but the mechanism by which an abuse history could influence the risk for BPD has not been determined. The aim of this study was to determine whether the tryptophan hydroxylase 1 (TPH1) gene is related to BPD in a clinical sample, and whether TPH1 genotypes or haplotypes moderate the relationship between abuse history and BPD.
  
  
  METHODS
  Three hundred and ninety-eight patients diagnosed with mood disorders were genotyped for TPH1 G-6526A promoter polymorphism (rs4537731) and the A218C intron 7 polymorphism (rs1800532) and a set of ancestry informative markers, assessed for Diagnostic and Statistical Manual of Mental Disorders, 4th edition diagnoses, and assessed for a history of physical and sexual abuse.
  
  
  RESULTS
  Patients with a diagnosis of BPD were more likely to be risk allele carriers (A alleles at both loci) than the non-BPD group. Logistic regression analysis predicting BPD diagnosis with both single-nucleotide polymorphisms and haplotypes showed significant interaction effects between genotype and abuse history. Poisson regression predicting the number of BPD diagnostic criteria met with the same predictor set also included a significant interaction term. Risk allele carriers with a history of abuse had an increased likelihood of a BPD diagnosis.
  
  
  CONCLUSIONS
  Variation in TPH1 may increase risk for developing BPD as a result of childhood abuse. Elements of BPD pathology may be due in part to a genetically influenced serotonergic dysfunction, which in turn may lead to a differential response to environmental stressors.
authors: Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY 10032, USA. stw16@columbia.edu
authors: Scott T
authors: ST
authors: Wilson
authors: Barbara
authors: B
authors: Stanley
authors: David A
authors: DA
authors: Brent
authors: Maria A
authors: MA
authors: Oquendo
authors: Yung-yu
authors: YY
authors: Huang
authors: Fatemeh
authors: F
authors: Haghighi
authors: Colin A
authors: CA
authors: Hodgkinson
authors: J John
authors: JJ
authors: Mann
mesh_terms: D000328:Adult; D001883:Borderline Personality Disorder / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D002648:Child; D002649:Child Abuse / Q000523:psychology*; D003710:Demography; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D014365:Tryptophan Hydroxylase / Q000235:genetics*
chemical_list: C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase