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Identification and functional validation of genetic variants in potential miRNA target sites of established BMI genes.
Kumar, Pankaj; Traurig, Michael; Baier, Leslie J.
Afiliação
  • Kumar P; Diabetes Molecular Genetics Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA.
  • Traurig M; Diabetes Molecular Genetics Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA.
  • Baier LJ; Diabetes Molecular Genetics Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA. lbaier@phx.niddk.nih.gov.
Int J Obes (Lond) ; 44(5): 1191-1195, 2020 05.
Article em En | MEDLINE | ID: mdl-31745258
OBJECTIVE: MicroRNAs (miRNAs) play an important role in posttranscriptional regulation by binding to target sites in the 3'UTR of protein-coding genes. Genetic variation within target sites may potentially disrupt the binding activity of miRNAs, thereby impacting this regulation. In the current study, we investigated whether any established BMI-associated genetic variants potentially function by altering a miRNA target site. METHODS: The genomic positions of all predicted miRNA target site seed regions were identified, and these positions were queried in the T2D Knowledge Portal for variants that associated with BMI in the GIANT UK Biobank. This in silico analysis identified ten target site variants that associated with BMI with a P value ≤ 5 × 10-8. These ten variants mapped to nine genes, FAIM2, CCDC171, ADPGK, ZNF654, MLXIP, NT5C2, SHISA4, SLC25A22, and CTNNB1. RESULTS: In vitro functional analyses showed that five of these target site variants, rs7132908 (FAIM2), rs4963153 (SLC25A22), rs9460 (ADPGK), rs11191548 (NT5C2), and rs3008747 (CCDC171), disrupted the binding activity of miRNAs to their target in an allele-specific manner. CONCLUSION: In conclusion, our study suggests that some established variants for BMI may function by altering miRNA binding to a 3'UTR target site.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Índice de Massa Corporal / Polimorfismo de Nucleotídeo Único / MicroRNAs / Obesidade Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Revista: Int J Obes (Lond) Assunto da revista: METABOLISMO Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Índice de Massa Corporal / Polimorfismo de Nucleotídeo Único / MicroRNAs / Obesidade Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Revista: Int J Obes (Lond) Assunto da revista: METABOLISMO Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos