Noncoding SNPs associated with increased GDF15 levels located in a metformin-activated enhancer region upstream of GDF15.
Pharmacogenomics
; 21(8): 509-520, 2020 06.
Article
em En
| MEDLINE
| ID: mdl-32427048
ABSTRACT
Aim:
GDF15 levels are a biomarker for metformin use. We performed the functional annotation of noncoding genome-wide association study (GWAS) SNPs for GDF15 levels and the Genotype-Tissue Expression (GTEx)-expression quantitative trait loci (eQTLs) for GDF15 expression within metformin-activated enhancers around GDF15. Materials &methods:
These enhancers were identified using chromatin immunoprecipitation followed by sequencing data for active (H3K27ac) and silenced (H3K27me3) histone marks on human hepatocytes treated with metformin, Encyclopedia of DNA Elements data and cis-regulatory elements assignment tools.Results:
The GWAS lead SNP rs888663, the SNP rs62122429 associated with GDF15 levels in the Outcome Reduction with Initial Glargine Intervention trial, and the GTEx-expression quantitative trait locus rs4808791 for GDF15 expression in whole blood are located in a metformin-activated enhancer upstream of GDF15 and tightly linked in Europeans and East Asians.Conclusion:
Noncoding variation within a metformin-activated enhancer may increase GDF15 expression and help to predict GDF15 levels.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo de Nucleotídeo Único
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Fator 15 de Diferenciação de Crescimento
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Estudo de Associação Genômica Ampla
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Metformina
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article