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Published in: BMC Medical Genetics 1/2012

Open Access 01-12-2012 | Research article

Expression analyses of the genes harbored by the type 2 diabetes and pediatric BMI associated locus on 10q23

Authors: Jianhua Zhao, Sandra Deliard, Ali Rahim Aziz, Struan FA Grant

Published in: BMC Medical Genetics | Issue 1/2012

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Abstract

Background

There is evidence that one of the key type 2 diabetes (T2D) loci identified by GWAS exerts its influence early on in life through its impact on pediatric BMI. This locus on 10q23 harbors three genes, encoding hematopoietically expressed homeobox (HHEX), insulin-degrading enzyme (IDE) and kinesin family member 11 (KIF11), respectively.

Methods

We analyzed the impact of adipogeneis on the mRNA and protein expression levels of these genes in the human adipocyte Simpson-Golabi-Behmel syndrome (SGBS) cell line in order to investigate which could be the culprit gene(s) in this region of linkage disequilibrium.

Results

Following activation of differentiation with a PPARγ ligand, we observed ~20% decrease in IDE, ~40% decrease in HHEX and in excess of 80% decrease in KIF11 mRNA levels when comparing the adipocyte and pre-adipocyte states. We also observed decreases in KIF11 and IDE protein levels, but conversely we observed a dramatic increase in HHEX protein levels. Subsequent time course experiments revealed some marked changes in expression as early as three hours after activation of differentiation.

Conclusion

Our data suggest that the expression of all three genes at this locus are impacted during SGBS adipogenesis and provides insights in to the possible mechanisms of how the genes at this 10q23 locus could influence both adipocyte differentiation and susceptibility to T2D through insulin resistance.
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Metadata
Title
Expression analyses of the genes harbored by the type 2 diabetes and pediatric BMI associated locus on 10q23
Authors
Jianhua Zhao
Sandra Deliard
Ali Rahim Aziz
Struan FA Grant
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2012
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-13-89

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