FTO Gene Affects Obesity and Breast Cancer Through Similar Mechanisms: A New Insight into the Molecular Therapeutic Targets

Akbari, ME; Gholamalizadeh, Maryam; Doaei, Saeid; Mirsafa, Faezeh

doi:10.1080/01635581.2018.1397709

Cited by 37 publications

(36 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is possible that the FTO gene polymorphism can modify the effects of diet on the FTO gene expression [ 28 ]. Although recent studies suggested that FTO has an effect on BMI, at least partly, through the change in the expression levels of other obesity-related genes such as IRX3 [ 29 – 30 ], Moreover, a complete LD was found in the present study between three neighboring SNPs of the first intron region of the FTO gene. Although the linkage disequilibrium (LD) between rs9930506, rs9930501 and rs9932754 has been reported in genome-wide association studies [ 22 , 31 , and 32 ].…”

Section: Discussioncontrasting

confidence: 72%

A haplotype of three SNPs in FTO had a strong association with body composition and BMI in Iranian male adolescents

et al. 2018

View full text Add to dashboard Cite

BackgroundSingle-nucleotide polymorphisms (SNPs), which are located in the first intron of the FTO gene, are reported to be associated with body weight and the body mass index (BMI). However, their effects on anthropometric measurements in adolescents are poorly understood.ObjectiveThis study aimed to investigate the association of three adjacent polymorphisms (rs9930506, rs9930501, & rs9932754) in the FTO gene with anthropometric indices in Iranian adolescent males.DesignThe participants comprised a total of 237 adolescent males who were recruited randomly from two high schools in Tehran, Iran. The DNA samples were genotyped for the FTO gene polymorphisms by DNA sequencing. BMI, body fat percentage (BF%), and body muscle percentage (BM%) were determined using a validated bioelectrical impedance analysis scale. The association of the FTO polymorphisms with weight, height, BMI, BF%, and BM% was investigated.ResultsA haplotype of rs9930506, rs9930501, and rs9932754 (GGT) in the first intron of the FTO with complete linkage disequilibrium (LD) was found to be significantly associated with higher weight (OR = 1.32), BMI (OR = 5.36) and BF% (OR = 1.46), and lower BM% (OR = 3.59) (all P<0.001). None of the students with GGC genotypes were underweight, while all of the students with AAT genotypes had high muscle mass.ConclusionsA haplotype in the first intron of the FTO gene had a strong association with obesity indices in Iranian adolescent males. The FTO gene polymorphisms might have greater effects on anthropometric indices than what was previously imagined. Moreover, we suggested that the FTO gene exerted their effects on anthropometric measurements through haplotypes (and not single SNPs).

show abstract

Section: Discussioncontrasting

confidence: 72%

A haplotype of three SNPs in FTO had a strong association with body composition and BMI in Iranian male adolescents

et al. 2018

View full text Add to dashboard Cite

show abstract

“…In another study carried out by Li et al, high expression of FTO with t(11q23) rearrangements has been observed to regulate the expression of ASB2 and RARA, leading to cell transformation and leukemogenesis in acute myeloid leukemia (AML) [88]. In addition, recently two different association studies by Salgado-Montilla et al in a cohort of Puerto Rican men and Akbari et al from literature survey, also reported causal link between FTO and cancer onset as well as progression [89, 90]. In a breast cancer biopsies study carried out by Zhang et al, a concordance of ALKBH5 and HIF-1a expression has been reported, suggesting hypoxia dependent regulation of ALKBH5.…”

Section: Alteration Of Modification Enzymes and Their Marks In Diseasesmentioning

confidence: 99%

Epitranscriptomic Code and Its Alterations in Human Disease

Kadumuri

Janga

2018

Trends in Molecular Medicine

113

126

View full text Add to dashboard Cite

Innovations in epitranscriptomics have resulted in the identification of more than 160 RNA modifications to date. These developments, together with the recent discovery of writers, readers, and erasers of modifications occurring across a wide range of RNAs and tissue types, have led to a surge in integrative approaches for transcriptome-wide mapping of modifications and protein-RNA interaction profiles of epitranscriptome players. RNA modification maps and crosstalk between them have begun to elucidate the role of modifications as signaling switches, entertaining the notion of an epitranscriptomic code as a driver of the post-transcriptional fate of RNA. Emerging single-molecule sequencing technologies and development of antibodies specific to various RNA modifications could enable charting of transcript-specific epitranscriptomic marks across cell types and their alterations in disease.

show abstract

“…A study by Guo and colleagues showed that FOXA2 overexpression was associated with significant downregulation of FTO promoter activity whereas FOXA2 depletion allowed FTO expression, thereby providing evidence that FOXA2 is a negative repressor of the FTO gene ( Guo et al, 2012 ). FTO was previously shown to be involved in several metabolic syndrome-related conditions such as diabetes, insulin signaling, lipogenesis, and mitochondrial dysfunction, whereby FTO overexpression was observed ( Bravard et al, 2011 ; Akbari et al, 2018 ). In this case, the lack of appropriate repressor response was associated with untimely expression of target genes, which resulted in clinical manifestation of diseases.…”

Section: Control Of Transcription By Trans-regulatory mentioning

confidence: 99%

Transcriptional regulation of metabolism in disease: From transcription factors to epigenetics

Hawkins

Al-attar

Storey

2018

PeerJ

View full text Add to dashboard Cite

Every cell in an individual has largely the same genomic sequence and yet cells in different tissues can present widely different phenotypes. This variation arises because each cell expresses a specific subset of genomic instructions. Control over which instructions, or genes, are expressed is largely controlled by transcriptional regulatory pathways. Each cell must assimilate a huge amount of environmental input, and thus it is of no surprise that transcription is regulated by many intertwining mechanisms. This large regulatory landscape means there are ample possibilities for problems to arise, which in a medical context means the development of disease states. Metabolism within the cell, and more broadly, affects and is affected by transcriptional regulation. Metabolism can therefore contribute to improper transcriptional programming, or pathogenic metabolism can be the result of transcriptional dysregulation. Here, we discuss the established and emerging mechanisms for controling transcription and how they affect metabolism in the context of pathogenesis. Cis- and trans-regulatory elements, microRNA and epigenetic mechanisms such as DNA and histone methylation, all have input into what genes are transcribed. Each has also been implicated in diseases such as metabolic syndrome, various forms of diabetes, and cancer. In this review, we discuss the current understanding of these areas and highlight some natural models that may inspire future therapeutics.

show abstract

FTO Gene Affects Obesity and Breast Cancer Through Similar Mechanisms: A New Insight into the Molecular Therapeutic Targets

Abstract: The FTO gene may has a critical role in obesity and breast cancer. Similar molecular mechanisms may play a role in the development of breast cancer and obesity. If this result is correct then, it will be interesting to examine the FTO gene as a molecular therapeutics target.

Cited by 37 publications

References 42 publications

A haplotype of three SNPs in FTO had a strong association with body composition and BMI in Iranian male adolescents

A haplotype of three SNPs in FTO had a strong association with body composition and BMI in Iranian male adolescents

Epitranscriptomic Code and Its Alterations in Human Disease

Transcriptional regulation of metabolism in disease: From transcription factors to epigenetics

Contact Info

Product

Resources

About