No Evidence for an Association of Polymorphisms of the Tryptophan Hydroxylase Gene With Affective Disorders or Attempted Suicide Among Japanese Patients

Kunugi, Hiroshi; Ishida, S; Kato, Tadafumi; Sakai, Toshiyuki; Tatsumi, Masahiko; Hirose, Tetsuya; Nanko, Shinichiro

doi:10.1176/ajp.156.5.774

Cited by 83 publications

(2 citation statements)

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“…Twenty-seven studies (4,917cases and 7,098 controls) assessed the relationship between TPH1 A218C polymorphism and the risk of suicide behavior ( 12 , 14 , 19 – 43 , 45 – 47 ). The integrated analyses demonstrated that the AA/AC genotypes of A218C polymorphism was significantly associated with an increased risk of SB compared with the CC genotype (OR = 1.11, 95%CI 1.01–1.22; P = 0.026, Q test = 0.212, I 2 = 19.90) ( Figure 2A ).…”

Section: Resultsmentioning

confidence: 99%

“…Thirteen studies (1,893 cases and 3,103 controls) assessed relationship between TPH1 A779C polymorphism and the risk of suicide behavior ( 11 , 14 , 15 , 24 , 28 – 30 , 32 , 33 , 35 , 44 , 46 , 47 ). Overall, we did not observe an association between A779C polymorphisms of TPH1 gene in the allele frequencies or any genotype model with an overall SB risk ( Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

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Association between TPH1 polymorphisms and the risk of suicide behavior: An updated meta-analysis of 18,398 individuals

et al. 2022

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ObjectivesWe aimed to examine the association of TPH1 polymorphisms with the risk of suicide behavior (SB).DesignSystematic review and meta-analysis.MethodAll relevant studies that evaluated the association between the A218C (rs1800532), A779C (rs1799913) and A6526G (rs4537731) polymorphisms and the susceptibility to SB published up to September 2021 were identified through a comprehensive systematic search in PubMed, Scopus, EBSCO and Science Direct electronic databases. The association between TPH1 gene polymorphisms and SB was evaluated using inherence models by odds ratio (OR) and 95% confidence interval (CI). Subgroup analyses, heterogeneity analyses, and publication bias were also tested in this meta-analysis.ResultsThe meta-analysis for TPH1 A218C revealed an increased risk of SB in the dominant model (OR = 1.11, 95%CI 1.01–1.22). We also observed a positive association in the allelic (OR = 1.13, 95%CI 1.05–1.21), homozygous (OR = 1.22, 95%CI 1.06–1.40), heterozygous (OR = 1.21, 95%CI 1.08–1.37) and dominant (OR = 1.21, 95%CI 1.09–1.34) inherence models with the suicide attempt. Additionally, in the heterozygous (OR = 0.84, 95%CI 0.73–0.97) and dominant (OR = 0.79, 95%CI 0.68–0.91) inherence models we detected an association with completed suicide. Based on ethnicity, an association of SB in the European population also was observed (OR = 1.29, 95%CI 1.12–1.51). However, for both A779C and A6526G polymorphisms we did not find evidence of an association with SB.ConclusionThis meta-analysis suggests that the A218C polymorphism of TPH1 gene could be a possible risk factor of SB. Future large-scale studies are required to analyze the molecular mechanisms by which affect the susceptibility of developing suicide behavior.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Association between TPH1 polymorphisms and the risk of suicide behavior: An updated meta-analysis of 18,398 individuals

et al. 2022

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Haplotype-Based Linkage of Tryptophan Hydroxylase 2 to Suicide Attempt, Major Depression, and Cerebrospinal Fluid 5-Hydroxyindoleacetic Acid in 4 Populations

Zhou

Roy²,

Lipsky³

et al. 2005

Arch Gen Psychiatry

189

159

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Association study of the tryptophan hydroxylase gene and bipolar affective disorder using family-based internal controls

Rietschel

Schorr

Albus³

et al. 2000

Am. J. Med. Genet.

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The tryptophan hydroxylase (TPH) gene encodes for the rate-limiting enzyme of the serotonin metabolism and, therefore, has to be considered a major candidate for association studies in affective disorders. Recently, an association between this gene and bipolar affective disorder has been reported in a French population. We sought to replicate this finding in a German sample. Allele frequencies of a biallelic polymorphism (A218C) of the TPH gene were determined in 95 bipolar I patients and their parents. Preferential transmission of alleles from heterozygous parents to bipolar offspring was tested with the "transmission disequilibrium test" (TDT), which eliminates the contribution of population stratification to an association finding. Our sample yielded a power >90% to detect the originally reported effect. Neither allele 218A nor allele 218C were preferentially transmitted from heterozygous parents to bipolar offspring. Our results, therefore, do not support the hypothesis that the TPH gene is involved in the etiology of bipolar disorder.

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No Evidence for an Association of Polymorphisms of the Tryptophan Hydroxylase Gene With Affective Disorders or Attempted Suicide Among Japanese Patients

Cited by 83 publications

References 6 publications

Association between TPH1 polymorphisms and the risk of suicide behavior: An updated meta-analysis of 18,398 individuals

Association between TPH1 polymorphisms and the risk of suicide behavior: An updated meta-analysis of 18,398 individuals

Haplotype-Based Linkage of Tryptophan Hydroxylase 2 to Suicide Attempt, Major Depression, and Cerebrospinal Fluid 5-Hydroxyindoleacetic Acid in 4 Populations

Association study of the tryptophan hydroxylase gene and bipolar affective disorder using family-based internal controls

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