Molecular and Gene Network Analysis of Thyroid Transcription Factor 1 (TTF1) and Enhanced at Puberty (EAP1) Genes in Patients with GnRH-Dependent Pubertal Disorders
Molecular and Gene Network Analysis of Thyroid Transcription Factor 1 (TTF1) and Enhanced at Puberty (EAP1) Genes in Patients with GnRH-Dependent Pubertal Disorders
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DOI：
10.1159/000354643
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发表时间：
2013-01-01
影响因子：
3.2
通讯作者：
Brito, Vinicius Nahime
中科院分区：
文献类型：
--
作者：
Cukier, Priscilla;Wright, Hollis;Brito, Vinicius Nahime
背景/目的：TTF1和EAP1是调节促性腺激素释放激素表达的转录因子。我们研究了TTF1和EAP1基因在中枢性青春期疾病中的作用。患者和方法：对133例中枢性青春期疾病患者进行研究，其中86例为中枢性早熟，47例为单纯性低促性腺激素低下症。对TTF1和EAP1的编码区进行了测序。用GeneScan软件分析EAP1基因中多聚谷氨酰胺和多丙氨酸重复序列的变异。应用Meta-Network框架GeneMANIA和Cytoscape软件研究TTF1和EAP1与青春期发育相关基因的相关性。结果：TTF1基因直接测序未发现任何突变或多态。4个EAP1同义变异体在不同群体中的频率相似。最常见的EAP1 5‘-末端聚丙氨酸基因型为纯合子12/12，但在2例中枢性性早熟姐妹中发现了12/9基因型，但EAP1转录活性无功能改变。TTF1和EAP1通过遗传网络与控制月经初潮的基因相连。结论：未发现TTF1或EAP1胚系突变与中枢性青春期疾病相关。TTF1和EAP1可能通过响应青春期相关基因网络的其他成员而改变表达，或者通过差异地影响这些网络的基因成分的表达来影响青春期。(C)2013年S.Karger AG，巴塞尔
Background/Aim: TTF1 and EAP1 are transcription factors that modulate gonadotropin-releasing hormone expression. We investigated the contribution of TTF1 and EAP1 genes to central pubertal disorders. Patients and Methods: 133 patients with central pubertal disorders were studied: 86 with central precocious puberty and 47 with normosmic isolated hypogonadotropic hypogonadism. The coding region of TTF1 and EAP1 were sequenced. Variations of polyglutamine and polyalanine repeats in EAP1 were analyzed by GeneScan software. Association of TTF1 and EAP1 to genes implicated in timing of puberty was investigated by meta-network framework GeneMANIA and Cytoscape software. Results: Direct sequencing of the TTF1 did not reveal any mutation or polymorphisms. Four EAP1 synonymous variants were identified with similar frequencies among groups. The most common EAP1 5'-distal polyalanine genotype was the homozygous 12/12, but the genotype 12/9 was identified in 2 central precocious puberty sisters without functional alteration in EAP1 transcriptional activity. TTF1 and EAP1 were connected, via genetic networks, to genes implicated in the control of menarche. Conclusion: No TTF1 or EAP1 germline mutations were associated with central pubertal disorders. TTF1 and EAP1 may affect puberty by changing expression in response to other members of puberty-associated gene networks, or by differentially affecting the expression of gene components of these networks. (C) 2013 S. Karger AG, Basel