Ishiguro H, Arinami T, Saito T, Akazawa S, Enomoto M, Mitushio H, Fujishiro H, Tada K, Akimoto Y, Mifune H, Shiozuka S, Hamaguchi H, Toru M, Shibuya H
Department of Neuropsychiatry, Tokyo Medical and Dental University School of Medicine, Japan.
Am J Med Genet. 1998 Sep 7;81(5):388-96.
Tyrosine hydroxylase is the rate-limiting step in the biosynthesis of catecholamines. To find variants in the tyrosine hydroxylase (TH) gene that are associated with schizophrenia, mood disorders, or alcohol dependence, all of the exons, the exon-intron boundaries, and the 5' promoter region of the TH gene were systematically screened for variants by single-strand conformation polymorphism analysis followed by direct nucleotide sequencing. Source DNAs for sequencing were from 88 Japanese patients comprised of 17 schizophrenics, 21 with mood disorders, and 50 alcoholics. Two novel variants, T-229A and Val468Met, were identified. Case-control comparisons demonstrated that distribution of these two variants were similar in the controls and the three psychiatric groups. Distributions of the previously reported Val81Met polymorphism alleles and the intron 1 TCAT repeat polymorphism alleles were similar in the four subject groups. Our study indicates that the TH gene is not likely to play a major role in the genetic predisposition to schizophrenia, mood disorders, or alcohol dependence.
酪氨酸羟化酶是儿茶酚胺生物合成中的限速步骤。为了寻找与精神分裂症、情绪障碍或酒精依赖相关的酪氨酸羟化酶（TH）基因变异，通过单链构象多态性分析随后直接进行核苷酸测序，对TH基因的所有外显子、外显子 - 内含子边界和5'启动子区域进行了系统的变异筛查。用于测序的来源DNA来自88名日本患者，其中包括17名精神分裂症患者、21名情绪障碍患者和50名酗酒者。鉴定出两个新的变异，T - 229A和Val468Met。病例对照比较表明，这两个变异在对照组和三个精神疾病组中的分布相似。先前报道的Val81Met多态性等位基因和内含子1 TCAT重复多态性等位基因在四个受试者组中的分布相似。我们的研究表明，TH基因不太可能在精神分裂症、情绪障碍或酒精依赖的遗传易感性中起主要作用。
