Association between neonatal temperament, SLC6A4, DRD4 and a functional polymorphism located in TFAP2B
Association between neonatal temperament, SLC6A4, DRD4 and a functional polymorphism located in TFAP2B
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DOI：
10.1111/j.1601-183x.2011.00696.x
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发表时间：
2011-07-01
影响因子：
2.5
通讯作者：
Molto, M. D.
中科院分区：
文献类型：
--
作者：
Ivorra, J. L.;D'Souza, U. M.;Molto, M. D.
迄今为止，关于人类人格的遗传学研究没有提供令人满意的结果，主要是因为这种特征的复杂性。新生儿气质的观察措施是一种替代表型接近遗传学的人类行为。对117名白人新生儿进行了相关研究。出生后48 h采用新生儿行为评定量表评定其气质。对SLC 6A 4、DRD 4和TFAP 2B基因的13个多态性进行了基因分型。进行线性回归分析数据，并应用Bonferroni校正。为了检查TFAP 2B插入缺失内含子2多态性的功能效应，使用小鼠皮质神经祖细胞系进行报告基因荧光素酶测定，并在人死后脑样品中进行定量聚合酶链反应（qPCR）研究。5-HTTLPR、5-HTTLPR + rs 25531和TFAP 2B Indel Intron 2与Range of State簇之间存在显著关联，rs 25531和TFAP 2B Indel Intron 2与Range of State簇之间存在相互作用。DRD 4可变数目串联重复序列外显子3与取向相关。使用pGL 3启动子载体发现TFAP 2B 5-重复等位基因的荧光素酶水平与6-重复等位基因相比增加了30%（P值= 0.03）。qPCR实验显示与体外研究相同的趋势，但未获得显著结果。本研究支持SLC 6A 4、DRD 4和TFAP 2B基因在气质中的作用，包括SLC 6A 4和TFAP 2B之间的基因-基因相互作用。这也提供了TFAP 2B基因转录中TFAP 2B多态性影响的证据。
Genetic studies on human personality have provided little satisfactory results to date mainly because of the complexity of this trait. Neonatal temperament using observational measures is an alternative phenotype to approach genetics to human behavior. An association study was conducted on 117 Caucasian newborns. Their temperament was evaluated using the Neonatal Behavior Assessment Scale 48 h after birth. Thirteen polymorphisms in the SLC6A4, DRD4 and TFAP2B genes were genotyped. Linear regression was performed to analyze data, and Bonferroni correction was applied. To check the functional effect of the TFAP2B Indel Intron 2 polymorphism, reporter gene luciferase assays using a mouse cortical neural progenitor cell line and quantitative polymerase chain reaction (qPCR) studies in human post-mortem brain samples were performed. A significant association was found between 5-HTTLPR, 5-HTTLPR + rs25531 and TFAP2B Indel Intron 2 with Range of State cluster as well as an interaction between rs25531 and TFAP2B Indel Intron 2 with Range of State. DRD4 variable number tandem repeat exon 3 was associated with orientation. A 30% increase in the luciferase levels of the TFAP2B 5-repeat alleles compared with the 6-repeat alleles (P-value = 0.03) was found using the pGL3 promoter vector. The qPCR experiments showed the same trend as the in vitro studies, although no significant results were obtained. This study supports a role of the SLC6A4, DRD4 and TFAP2B genes in the temperament, including a gene-gene interaction between SLC6A4 and TFAP2B. It also provides evidence about an effect of the TFAP2B polymorphism in TFAP2B gene transcription.