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肥胖和超重男青少年进行强化生活方式干预后 FTO 和 IRX3 基因表达的变化及 FTO 基因型在此相互作用中的作用。

Changes in FTO and IRX3 gene expression in obese and overweight male adolescents undergoing an intensive lifestyle intervention and the role of FTO genotype in this interaction.

机构信息

Research Center of Health and Environment, Guilan University of Medical Sciences, Rasht, Iran.

Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

J Transl Med. 2019 May 24;17(1):176. doi: 10.1186/s12967-019-1921-4.

Abstract

BACKGROUND

Lifestyle intervention may have a critical effect on the association between genetics and obesity. This study aimed to investigate changes in FTO and IRX3 gene expression in obese and overweight male adolescents undergoing a lifestyle intervention and the role of FTO genotype in this interaction.

METHODS

This study was a field trial of 62 adolescents from boys' high schools in Tehran, Iran. Two schools were randomly allocated as the intervention (n = 30) and control (n = 32) schools. The rs9930506 SNP in FTO was genotyped at baseline and the level of FTO and IRX3 expression in peripheral blood mononuclear cells (PBMCs). Anthropometric measurements were assessed at baseline and after 18 weeks of intensive lifestyle intervention.

RESULTS

Our results showed that IRX3 expression in the intervention group was significantly up-regulated compared to baseline (P = 0.007) and compared to the control group (P = 0.011).The intervention group had significantly up-regulated transcripts of IRX3 only in rs9930506 risk allele carriers of the intervention group compared to risk allele carriers of the control group (P = 0.017). Moreover, our data showed that the FTO expression was up-regulated in AA genotype carriers and down-regulated in AG/GG genotype carriers (P = 0.017).

CONCLUSION

Lifestyle modification may exert its effects on obesity through changes in the expression level of the FTO and IRX3 genes. However, FTO genotype plays a role in the extent of the effect of lifestyle changes on gene expression. Further studies are crucial to have a better understanding of the interaction between lifestyle, genetics and anthropometric measurements. Trial registration This paper reports a comprehensive intervention study (Interactions of Genetics, Lifestyle and Anthropometrics study or IGLA study), which is retrospectively registered in the Iranian Registry of Clinical Trials as IRCT2016020925699N2. Date registered: April 24, 2016. ( https://www.irct.ir/searchresult.php?id=25699&number=2 ).

摘要

背景

生活方式干预可能对遗传与肥胖之间的关联产生重大影响。本研究旨在探讨肥胖和超重男性青少年在接受生活方式干预后 FTO 和 IRX3 基因表达的变化,以及 FTO 基因型在这种相互作用中的作用。

方法

这是一项在伊朗德黑兰男校青少年中进行的现场试验。两所学校被随机分配为干预组(n=30)和对照组(n=32)。在基线时对 FTO 中的 rs9930506 SNP 进行基因分型,并检测外周血单核细胞(PBMC)中 FTO 和 IRX3 的表达水平。在基线和 18 周的强化生活方式干预后评估人体测量学测量值。

结果

我们的结果表明,与基线相比(P=0.007)和与对照组相比(P=0.011),干预组的 IRX3 表达显著上调。与对照组风险等位基因携带者相比,仅在干预组的 rs9930506 风险等位基因携带者中,干预组的 IRX3 转录物显著上调(P=0.017)。此外,我们的数据表明,FTO 表达在 AA 基因型携带者中上调,在 AG/GG 基因型携带者中下调(P=0.017)。

结论

生活方式改变可能通过改变 FTO 和 IRX3 基因的表达水平对肥胖产生影响。然而,FTO 基因型在生活方式改变对基因表达的影响程度上发挥作用。进一步的研究对于更好地理解生活方式、遗传和人体测量学之间的相互作用至关重要。

试验注册

本文报道了一项综合干预研究(遗传、生活方式和人体测量相互作用研究或 IGLA 研究),该研究在伊朗临床试验注册中心(IRCT)中作为 IRCT2016020925699N2 进行了回顾性注册。注册日期:2016 年 4 月 24 日。(https://www.irct.ir/searchresult.php?id=25699&number=2)。

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