Further clarification of the contribution of the tryptophan hydroxylase (TPH) gene to suicidal behavior using systematic allelic and genotypic meta-analyses
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Suicide is a major public health issue, especially in western countries, accounting for approximately 1 million deaths every year throughout the world. The tryptophan hydroxylase (TPH) gene has been extensively studied as a candidate for suicidal behavior due to its role in serotonergic neurotransmission. Since the first study associating the gene with schizophrenia, there have been many attempts to replicate it. However, a number of these studies have produced contrary results, possibly reflecting inadequate statistical power and the use of different populations. Association data relating European and, more particularly, Asian populations has become increasingly available in recent years. To examine whether the aggregate data provide evidence of statistical significance, the current meta-analysis has combined all the published studies up to July 2005, and examined the polymorphisms (A779C, A218C, A-6526G) in the context of varied suicidal behaviors by analyzing the studies in total and in subsets. Compared with the inconsistent results of previous studies, the current results (22 references) confirm a strong overall association between suicidal behavior and the A779C/A218C polymorphisms, supporting the involvement of TPH in the pathogenesis of suicidal behavior.
KeywordsMeta-analysis Association Suicide Tryptophan hydroxylase (TPH)
This work was supported by grants from the Ministry of Education, PRC, the national 973 and 863 programs, the National Natural Science Foundation of China, and the Shanghai Municipal Commission for Science and Technology.
- Faludi G, Du L, Palkovits M, Antal B, Sotonyi P, Hrdina PD (2000) Serotonin transporter, serotonin-2A receptor and tryptophan hydroxilase gene polymorphisms in depressed suicide victims. Neurobiology (Bp) 8:269–271Google Scholar
- Gelernter J, Kranzler H, Lacobelle J (1998) Population studies of polymorphisms at loci of neuropsychiatric interest (tryptophan hydroxylase (TPH), dopamine transporter protein (SLC6A3), D3 dopamine receptor (DRD3), apolipoprotein E (APOE), mu opioid receptor (OPRM1), and ciliary neurotrophic factor (CNTF)). Genomics 52:289–297PubMedCrossRefGoogle Scholar
- Han L, Nielsen DA, Rosenthal NE, Jefferson K, Kaye W, Murphy D, Altemus M, Humphries J, Cassano G, Rotondo A, Virkkunen M, Linnoila M, Goldman D (1999) No coding variant of the tryptophan hydroxylase gene detected in seasonal affective disorder, obsessive-compulsive disorder, anorexia nervosa, and alcoholism. Biol Psychiatry 45:615–619PubMedCrossRefGoogle Scholar
- Souery D, Van Gestel S, Massat I, Blairy S, Adolfsson R, Blackwood D, Del-Favero J, Dikeos D, Jakovljevic M, Kaneva R, Lattuada E, Lerer B, Lilli R, Milanova V, Muir W, Nothen M, Oruc L, Papadimitriou G, Propping P, Schulze T, Serretti A, Shapira B, Smeraldi E, Stefanis C, Thomson M, Van Broeckhoven C, Mendlewicz J (2001) Tryptophan hydroxylase polymorphism and suicidality in unipolar and bipolar affective disorders: a multicenter association study. Biol Psychiatry 49:405–409PubMedCrossRefGoogle Scholar
- Staner L, Uyanik G, Correa H, Tremeau F, Monreal J, Crocq MA, Stefos G, Morris-Rosendahl DJ, Macher JP (2002) A dimensional impulsive-aggressive phenotype is associated with the A218C polymorphism of the tryptophan hydroxylase gene: a pilot study in well-characterized impulsive inpatients. Am J Med Genet 114:553–557PubMedCrossRefGoogle Scholar
- Zalsman G, Frisch A, King RA, Pauls DL, Grice DE, Gelernter J, Alsobrook J, Michaelovsky E, Apter A, Tyano S, Weizman A, Leckman JF (2001) Case control and family-based studies of tryptophan hydroxylase gene A218C polymorphism and suicidality in adolescents. Am J Med Genet 105:451–457PubMedCrossRefGoogle Scholar