FAM13A and POM121C are candidate genes for fasting insulin: functional follow-up analysis of a genome-wide association study

Diabetologia
Veroniqa LundbäckIngrid Dahlman

Abstract

By genome-wide association meta-analysis, 17 genetic loci associated with fasting serum insulin (FSI), a marker of systemic insulin resistance, have been identified. To define potential culprit genes in these loci, in a cross-sectional study we analysed white adipose tissue (WAT) expression of 120 genes in these loci in relation to systemic and adipose tissue variables, and functionally evaluated genes demonstrating genotype-specific expression in WAT (eQTLs). Abdominal subcutaneous adipose tissue biopsies were obtained from 114 women. Basal lipolytic activity was measured as glycerol release from adipose tissue explants. Adipocytes were isolated and insulin-stimulated incorporation of radiolabelled glucose into lipids was used to quantify adipocyte insulin sensitivity. Small interfering RNA-mediated knockout in human mesenchymal stem cells was used for functional evaluation of genes. Adipose expression of 48 of the studied candidate genes associated significantly with FSI, whereas expression of 24, 17 and 2 genes, respectively, associated with adipocyte insulin sensitivity, lipolysis and/or WAT morphology (i.e. fat cell size relative to total body fat mass). Four genetic loci contained eQTLs. In one chromosome 4 locus (rs38220...Continue Reading

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Citations

Mar 21, 2020·Nature Communications·Mohsen FathzadehJoshua W Knowles
May 16, 2019·Scientific Reports·Julia MorrisRona J Strawbridge
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Jan 8, 2021·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·H ZhouQ Wang

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Methods Mentioned

BETA
ELISA
lipolysis

Software Mentioned

Ensemble
QLUCORE R
SNPnexus
GTEx
Ingenuity Pathway Analysis
JJMP

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