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味觉受体、先天免疫与长寿:以TAS2R16基因为例

Taste receptors, innate immunity and longevity: the case of TAS2R16 gene.

作者信息

Malovini Alberto, Accardi Giulia, Aiello Anna, Bellazzi Riccardo, Candore Giuseppina, Caruso Calogero, Ligotti Mattia Emanuela, Maciag Anna, Villa Francesco, Puca Annibale A

机构信息

Laboratory of Informatics and Systems Engineering for Clinical Research, Istituti Clinici Scientifici Maugeri, 27100 Pavia, Italy.

2Section of General Pathology, Department of Biomedicine, Neurosciences and Advanced Technologies, University of Palermo, Corso Tukory 211, 90134 Palermo, Italy.

出版信息

Immun Ageing. 2019 Feb 23;16:5. doi: 10.1186/s12979-019-0146-y. eCollection 2019.

Abstract

BACKGROUND

Innate immunity utilizes components of sensory signal transduction such as bitter and sweet taste receptors. In fact, empirical evidence has shown bitter and sweet taste receptors to be an integral component of antimicrobial immune response in upper respiratory tract infections. Since an efficient immune response plays a key role in the attainment of longevity, it is not surprising that the rs978739 polymorphism of the bitter taste receptor TAS2R16 gene has been shown to be associated with longevity in a population of 941 individuals ranging in age from 20 to 106 years from Calabria (Italy). There are many possible candidate genes for human longevity, however of the many genes tested, only APOE and FOXO3 survived to association in replication studies. So, it is necessary to validate in other studies genes proposed to be associated with longevity. Thus, we analysed the association of the quoted polymorphism in a population of long lived individuals (LLIs) and controls from another Italian population from Cilento.

METHODS

The analysis has been performed on data previously obtained with genome-wide association study on a population of LLIs (age range 90-109 years) and young controls (age range 18-45 years) from Cilento (Italy).

RESULTS

Statistical power calculations showed that the analysed cohort represented by 410 LLIs and 553 young controls was sufficiently powered to replicate the association between rs978739 and the longevity phenotype according to the effect size and frequencies described in the previous paper, under a dominant and additive genetic model. However, no evidence of association between rs978739 and the longevity phenotype was observed according to the additive or dominant model.

CONCLUSION

There are several reasons for the failure of the confirmation of a previous study. However, the differences between the two studies in terms of environment of the population adopted and of the criteria of inclusion have made difficult the replication of the findings.

摘要

背景

固有免疫利用诸如苦味和甜味受体等感觉信号转导成分。事实上,已有实验证据表明苦味和甜味受体是上呼吸道感染中抗菌免疫反应的一个组成部分。由于有效的免疫反应在长寿的实现中起着关键作用,因此苦味受体TAS2R16基因的rs978739多态性与来自意大利卡拉布里亚的941名年龄在20至106岁人群的长寿相关也就不足为奇了。人类长寿有许多可能的候选基因,然而在众多测试基因中,只有载脂蛋白E(APOE)和叉头框蛋白O3(FOXO3)在重复研究中仍保持关联。所以,有必要在其他研究中验证那些被认为与长寿相关的基因。因此,我们分析了来自意大利奇伦托另一人群的长寿个体(LLIs)和对照人群中上述多态性的关联性。

方法

分析的数据先前通过全基因组关联研究获得,该研究针对来自意大利奇伦托的长寿个体(年龄范围90 - 109岁)和年轻对照(年龄范围18 - 45岁)人群。

结果

统计效能计算表明,根据前一篇论文中描述的效应大小和频率,在显性和加性遗传模型下,由410名长寿个体和553名年轻对照组成的分析队列有足够的效能来重复rs978739与长寿表型之间的关联。然而,根据加性或显性模型,未观察到rs978739与长寿表型之间存在关联的证据。

结论

先前研究未能得到证实有多种原因。然而,两项研究在采用的人群环境和纳入标准方面的差异使得研究结果难以重复。

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