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Association of TPH1 with suicidal behaviour and psychiatric disorders in the Chinese population
  1. X Liu1,2,
  2. H Li3,
  3. W Qin1,2,
  4. G He1,2,
  5. D Li1,2,
  6. Y Shen3,
  7. J Shen4,
  8. N Gu3,
  9. G Feng3,
  10. L He2,5
  1. 1Bio-X Life Science Research Center, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China
  2. 2Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, China
  3. 3Shanghai Institute of Mental Health, 600 South Wanping Road, Shanghai 200030, China
  4. 4Center for Neurologic Diseases, Brigham and Women’s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
  5. 5NHGG, Bio-X Center, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China
  1. Correspondence to:
 Dr L He
 Shanghai Jiao Tong University, Haoran Building, Bio-X Center, 1954 Huashan Road, Shanghai 200030, China or Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, China; helin{at}nhgg.org

Abstract

Tryptophan hydroxylase (TPH), the rate limiting enzyme in serotonin biosynthesis, is one of the most important regulating factors in the serotonergic system. Recently, polymorphisms of the TPH gene have been identified as being associated with suicide, but the evidence is inconsistent. To investigate the role in suicide of one of the isoforms, TPH1, we examined the association of five single nucleotide polymorphisms (SNPs) in the promoter region and in intron 7 of the TPH1 gene based on a sample from the Chinese population of 810 subjects, of whom 329 had made no suicide attempts (NSA), 297 had made suicide attempts (SA), and 184 were healthy subjects (HS). In this study, we observed statistically significant differences between NSA and HS subjects in allele distributions on one marker, −6526A (p = 0.0329; odds ratio (OR) 1.36; 95% confidence interval (CI) 1.01 to 1.81). No significant difference in genotype distribution or allele frequencies of other polymorphisms was found between the suicide victims and the controls. The overall haplotype frequency was significantly different between cases and healthy controls (p = 0.000024 NSA v HS; p<0.000001, SA v HS; p<0.000001, cases v HS). We found the haplotype TCAAA of −7180/−7065/−6526/218/779 to be strongly associated with suicidal behaviour and psychiatric disorders (p = 0.00243; OR = 1.62; 95% CI 1.17 to 2.24 and p = 0.018; OR = 1.41; 95% CI 1.05 to 1.91), which suggests an association of TPH1 with suicidal behaviour and indicates that TPH1 may play a significant role in the aetiology of psychiatric disorders in the Han Chinese population.

  • 5-HIAA, 5-hydroxyindoleacetic acid
  • HS, healthy subjects
  • LD, linkage disequilibrium
  • NSA, no suicide attempts
  • SA, suicide attempts
  • SNP, single nucleotide polymorphism
  • TPH, tryptophan hydroxylase
  • UNG, uracil-N-glycosylase
  • schizophrenia
  • TPH1
  • haplotype
  • suicide
  • Han Chinese

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Footnotes

  • The first three authors contributed equally to this work.

  • Competing interests: there are no competing interests.

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