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The FTO Gene and Diseases: The Role of Genetic Polymorphism, Epigenetic Modifications, and Environmental Factors
Russian Journal of Genetics ( IF 0.6 ) Pub Date : 2020-09-23 , DOI: 10.1134/s1022795420090136
A. N. Kucher

Abstract

The review provides information on the function of the FTO gene (known as the fat mass and obesity-associated gene) and the encoded enzyme, on the functional role of single nucleotide polymorphisms (SNPs) in coding and noncoding gene regions and the range of their competences, and on association of the FTO polymorphisms with diseases and traits. Factors that have modifying effect on the contribution of polymorphisms to the risk of disease development and trait variability are discussed. The FTO gene encodes alpha-ketoglutarate-dependent dioxygenase, which has a wide range of competences (including demethylation of RNA and single-stranded DNA), which are important for the functioning of the body. Nonsynonymous substitutions in the FTO gene lead to the development of orphan autosomal recessive disease (OMIM 612938). In the FTO noncoding regions, a wide range of variants has been detected, including those of regulatory importance (eQTL, sQTL, etc.). The competence of these variants extends to both FTO and neighboring genes (IRX3, IRX5, RPGRIP1L). Intronic polymorphisms of the FTO gene have been found to be associated with a wide range of multifactorial diseases and traits (obesity and related anthropometric traits, lipid metabolism markers, diabetes mellitus (type 2), coronary heart disease, metabolic syndrome, and other diseases). In the overwhelming majority of studies, the same allele variants are classified as risk ones; however, previously established associations of the FTO polymorphisms with diseases (traits) are demonstrated not in all populations. It is demonstrated that the effects of the FTO gene SNPs can be modified by exogenous and endogenous environmental factors, as well as lifestyle (including the type of diet, consumption of certain nutrients and medications, physical activity, etc.). Epigenetic factors (DNA methylation at CpG sites) are also important for regulating the level of FTO expression and the effects of individual SNPs. The accumulated data on the FTO structure and function, as well as the functional role of the encoded enzyme, make this gene attractive from the point of view of developing personalized approaches to healthcare.



中文翻译:

FTO基因和疾病:遗传多态性,表观遗传修饰和环境因素的作用。

摘要

该综述提供了有关FTO基因(称为脂肪和肥胖相关基因)和编码酶的功能,单核苷酸多态性(SNP)在编码和非编码基因区域中的功能作用及其范围的信息。能力,以及FTO多态性与疾病和性状的关联。讨论了影响多态性对疾病发展和性状变异风险的贡献的因素。的FTO基因编码α-酮戊二酸依赖性双加氧酶,其具有宽范围的能力(包括RNA的去甲基化和单链DNA),其是用于所述主体的所述功能是重要的。FTO中的非同义替换基因导致孤儿常染色体隐性遗传疾病的发展(OMIM 612938)。在FTO非编码区域中,已检测到多种变体,包括具有法规重要性的变体(eQTL,sQTL等)。这些变体的能力延伸到FTO和邻近基因(IRX3IRX5RPGRIP1L)。FTO的内含子多态性已发现该基因与多种多因素疾病和特征(肥胖症和相关人体测量学特征,脂质代谢标志物,糖尿病(2型),冠心病,代谢综合征和其他疾病)有关。在绝大多数研究中,相同的等位基因变异被归类为风险变异。但是,并非所有人群都证明了先前建立的FTO多态性与疾病(特征)的关联。事实证明,FTO的影响基因SNP可以通过外源性和内源性环境因素以及生活方式(包括饮食类型,某些营养物质和药物的消耗,身体活动等)进行修饰。表观遗传因素(CpG位点的DNA甲基化)对于调节FTO表达水平和单个SNP的作用也很重要。从开发个性化保健方法的观点来看,有关FTO结构和功能以及所编码酶的功能作用的累积数据使该基因具有吸引力。

更新日期:2020-09-23
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