Investigation of tryptophan hydroxylase 2 (TPH2) in schizophrenia and in the response to antipsychotics.
Investigation of tryptophan hydroxylase 2 (TPH2) in schizophrenia and in the response to antipsychotics.
复制标题
色氨酸羟化酶 2 (TPH2) 在精神分裂症和抗精神病药物反应中的研究
DOI：
10.1016/j.jpsychires.2012.04.021
复制
发表时间：
2012
影响因子：
4.8
通讯作者：
Häfner H.
中科院分区：
文献类型：
--
作者：
Schuhmacher A;Becker T;Rujescu D;Lennertz L;Wagner M;Quednow B.B;Benninghoff J;Rietschel M;Häfner H.
血清素能传递被认为与精神分裂症的病理生理学和治疗相关。色氨酸羟化酶（TPH）是血清素生物合成中的限速酶。虽然 TPH1 基因已被发现与精神分裂症相关，但针对 TPH2 变异的研究并未得出关于精神分裂症或抗精神病药物反应的结论性结果。我们分析了两个病例对照样本中的 11 个 TPH2 SNP，该样本总共包含 4453 名个体。选择了 6 个 SNP，因为它们具有潜在的功能相关性（rs4570625、rs11178997、rs11178998、rs7954758、rs7305115 和 rs4290270），并得到基于 HapMap LD 信息选择的另外 5 个标记 SNP 的支持。在发现样本（1476 名个体）中，我们观察到 rs10784941（p = 0.009，或次要 G 等位基因 0.82 [0.71–0.95]）和 rs4565946（p = 0.011，或次要 T 等位基因 0.83 [0.71–0.96]）与精神分裂症显着相关。还观察到与常见 rs4570625–rs4565946 单倍型的关联（OR G-C 单倍型 1.20 [1.02–1.40]；p = 0.0046）。单标记关联无法在由 2977 个个体组成的复制样本中复制，但 rs4570625–rs4565946 G-C 单倍型存在强烈趋势（OR 1.10 [0.98–1.24]；p（单边检验）= 0.054）。在较小的子样本中，罕见的 rs4570625–rs4565946 T-T 单倍型与精神分裂症患者的处理速度降低（n = 193，p = 0.004）和感觉运动门控（n = 68，p = 0.006）相关。在使用精神分裂症阳性和阴性症状量表 (PANSS) 治疗 4 周后，TPH2 变异和 rs4570625–rs4565946 G-C 单倍型不会影响抗精神病药物 (n = 210) 的有益反应。我们还研究了 SNP 与治疗反应的关联，但没有得到显着的结果。总之，我们的结果表明 TPH2 在精神分裂症中只发挥很小的作用。
Serotonergic transmission is considered relevant in the pathophysiology and the treatment of schizophrenia. Tryptophan hydroxylase (TPH) is the rate limiting enzyme in the biosynthesis of serotonin. While the TPH1 gene has been found to be associated with schizophrenia, studies focusing on TPH2 variants did not yield conclusive results for schizophrenia or the response to antipsychotic medication. We analyzed eleven TPH2 SNPs in two case–control samples consisting of 4453 individuals in total. Six SNPs were selected because of their potential functional relevance (rs4570625, rs11178997, rs11178998, rs7954758, rs7305115, and, rs4290270) and were supported by another 5 tagging SNPs selected based on HapMap LD information. In the discovery sample (1476 individuals), we observed a significant association with schizophrenia for rs10784941 (p = 0.009, OR minor G-allele 0.82 [0.71–0.95]) and rs4565946 (p = 0.011, OR minor T-allele 0.83 [0.71–0.96]). Association was also observed with a common rs4570625–rs4565946 haplotype (OR G-C haplotype 1.20 [1.02–1.40]; p = 0.0046). Single-marker associations could not be replicated in the replication sample consisting of 2977 individuals, but there was a strong trend regarding the rs4570625–rs4565946 G-C haplotype (OR 1.10 [0.98–1.24]; p(one-sided test) = 0.054). In smaller sub-samples, the rare rs4570625–rs4565946 T-T haplotype was associated with reduced processing speed (n = 193, p = 0.004) and sensorimotor gating (n = 68, p = 0.006) of schizophrenia patients. TPH2 variants and the rs4570625–rs4565946 G-C haplotype did not influence the beneficial response to antipsychotic drugs (n = 210) after four weeks of treatment administering the Positive and Negative Syndrome Scale of Schizophrenia (PANSS). We also investigated the association of the SNPs to treatment response, but did not get significant results. In sum, our results argue for only a minor role of TPH2 in schizophrenia.
登录
查看更多内容
影响因子：
11
作者：
Baehne, C. G.;Ehlis, A-C;Fallgatter, A. J.
通讯作者：
Fallgatter, A. J.
自杀受害者中新型色氨酸羟化酶异构体（TPH2）基因的单核苷酸多态性和单倍型分析
影响因子：
10.6
作者：
P. Zill;A. Büttner;W. Eisenmenger;H. Möller;B. Bondy;M. Ackenheil
通讯作者：
M. Ackenheil
利培酮或氟哌啶醇短期治疗首发精神分裂症：德国精神分裂症研究网络随机对照试验的 8 周结果。
DOI：
10.1017/s1461145708008791
发表时间：
2008
期刊：
The international journal of neuropsychopharmacology
影响因子：
--
作者：
H. Möller;M. Riedel;M. Jäger;Florian Wickelmaier;W. Maier;K. Kühn;G. Buchkremer;I. Heuser;J. Klosterkötter;M. Gastpar;D. Braus;R. Schlösser;F. Schneider;C. Ohmann;M. Riesbeck;W. Gaebel
通讯作者：
W. Gaebel
5-HT2A 受体多态性影响精神分裂症患者的感觉运动门控
影响因子：
10.6
作者：
B. Quednow;K. Kühn;R. Mössner;S. Schwab;A. Schuhmacher;W. Maier;M. Wagner
通讯作者：
M. Wagner
影响因子：
5.3
作者：
R. Shelton;M. Trivedi
通讯作者：
M. Trivedi