Galfalvy Hanga, Huang Yung-Yu, Oquendo Maria A, Currier Dianne, Mann J John
Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University,; and New York State Psychiatric Institute, New York, NY 10032, USA.
J Affect Disord. 2009 Jun;115(3):331-8. doi: 10.1016/j.jad.2008.09.019. Epub 2008 Oct 31.
The tryptophan hydroxylase 1 (TPH1) gene is reported to be associated with suicidal behavior. This has not been confirmed by prospective studies of suicide and clinical or biological mediators of this genetic risk have not been identified.
343 subjects (Caucasian, African-American, Hispanic) presenting with a Major Depressive Episode were genotyped for polymorphisms A218C in intron 7 and A-6526G in the promoter region of TPH1, and monitored for suicide attempts for up to one year. Clinical correlates of suicidal behavior and CSF-HIAA, HVA and MHPG levels were explored as possible mediators of genetic risk. Analyses were adjusted for ethnicity.
The AA genotype on intron 7 and the AA genotype on the promoter (both more prevalent in Caucasians) predicted suicide attempts during the 1 year follow-up, and were associated with past attempts of high medical lethality, regardless of ethnicity. The intron 7 genotype was associated with fewer reported reasons for living, and lower impulsivity. Haplotype analysis indicated significant increase in risk of suicide attempts for subjects with four risk alleles. TPH1 genotype was not associated with CSF metabolite levels.
The TPH1 gene is likely one of several genes associated with suicidal behavior. Power to detect differential genotype effects by ethnicity is low.
Polymorphisms of TPH1 may assist in identifying a subgroup of mood disorder patients that is at higher risk for suicidal behavior.
据报道，色氨酸羟化酶1（TPH1）基因与自杀行为有关。但这尚未得到自杀前瞻性研究的证实，且该遗传风险的临床或生物学介导因素尚未明确。
对343名患有重度抑郁发作的受试者（白种人、非裔美国人、西班牙裔）进行TPH1基因第7内含子A218C多态性和启动子区域A - 6526G多态性的基因分型，并对其自杀企图进行长达一年的监测。探讨自杀行为与脑脊液5 - 羟吲哚乙酸（CSF - HIAA）、高香草酸（HVA）和3 - 甲氧基 - 4 -羟基苯乙二醇（MHPG）水平的临床相关性，作为遗传风险的可能介导因素。分析针对种族进行了校正。
第7内含子的AA基因型和启动子的AA基因型（在白种人中更为常见）在1年随访期间预测了自杀企图，且与过去高医疗致死性的企图相关，与种族无关。第7内含子基因型与报告的生存理由较少以及较低的冲动性相关。单倍型分析表明，具有四个风险等位基因的受试者自杀企图风险显著增加。TPH1基因型与脑脊液代谢物水平无关。
TPH1基因可能是与自杀行为相关的多个基因之一。按种族检测不同基因型效应的效能较低。
TPH1基因多态性可能有助于识别自杀行为风险较高的情绪障碍患者亚组。
