Zaboli Ghazal, Jönsson Erik G, Gizatullin Rinat, Asberg Marie, Leopardi Rosario
Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute and Hospital, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
Biol Psychiatry. 2006 Sep 15;60(6):563-9. doi: 10.1016/j.biopsych.2006.03.033. Epub 2006 Jun 27.
Serotonin (5-HT) has been implicated in the pathophysiology of schizophrenia. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of serotonin (5-HT), and as such it might be related to the pathogenesis of schizophrenia. Two isoforms are known, TPH-1 and TPH-2. TPH-1 association with schizophrenia is debated.
A case-control design was employed for gene-disease association in 155 schizophrenic psychosis patients and 253 healthy controls, all North European Caucasians. Six single nucleotide polymorphisms (SNPs) with a haplotype block structure spanning over 23 kb of the total TPH-1 29 kb were analyzed. Linkage disequilibrium and haplotype analyses were performed. Bonferroni correction was used for multiple testing.
Single marker association analyses showed two SNPs significantly associated with schizophrenia. Several haplotypes were associated with the disease. A "sliding window" analysis attributed the strongest disease association to a haplotype configuration localized between the promoter region and intron 3.
Our data indicate that TPH-1 associates with schizophrenia. It appears that specific combinations of promoter variants vis-à-vis gene transcript variants contribute to genetic predisposition to the disease.
血清素（5-羟色胺，5-HT）与精神分裂症的病理生理学有关。色氨酸羟化酶（TPH）是血清素（5-HT）生物合成中的限速酶，因此它可能与精神分裂症的发病机制有关。已知有两种同工型，即TPH-1和TPH-2。TPH-1与精神分裂症的关联存在争议。
采用病例对照设计，对155例精神分裂症精神病患者和253名健康对照者进行基因-疾病关联研究，所有受试者均为北欧白种人。分析了6个单核苷酸多态性（SNP），其单倍型结构跨越TPH-1全长29 kb中的23 kb。进行了连锁不平衡和单倍型分析。采用Bonferroni校正进行多重检验。
单标记关联分析显示，有两个SNP与精神分裂症显著相关。几种单倍型与该疾病相关。“滑动窗口”分析表明，最强的疾病关联归因于位于启动子区域和内含子3之间的单倍型构型。
我们的数据表明TPH-1与精神分裂症有关。启动子变体与基因转录变体的特定组合似乎有助于疾病的遗传易感性。
