Article

Cotsapas, C., Prokunina-Olsson L., Welch C., Saxena R., Weaver C., Usher N., Guiducci C., Bonakdar S., Turner N., LaCroix B., and Hall JL. 2010. Expression analysis of loci associated with type 2 diabetes in human tissues. Diabetologia 53: 2334-39.

Department of Medicine, Harvard Medical School, Boston, MA USA; Developmental Biology Center, University of Minnesota, Minneapolis, MN USA; Center for Human Genetic Research, Department of Medicine, Massachusetts General Hospital, Boston, MA USA; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA USA
Diabetologia (Impact Factor: 6.49). 11/2010; 53:2334-39. DOI: 10.1007/s00125-010-1861-2
Source: PubMed

ABSTRACT Genetic mapping has identified over 20 loci contributing to genetic risk of type 2 diabetes. The next step is to identify the genes and mechanisms regulating the contributions of genetic risk to disease. The goal of this study was to evaluate the effect of age, height, weight and risk alleles on expression of candidate genes in diabetes-associated regions in three relevant human tissues.
METHODS:
We measured transcript abundance for WFS1, KCNJ11, TCF2 (also known as HNF1B), PPARG, HHEX, IDE, CDKAL1, CDKN2A, CDKN2B, IGF2BP2, SLC30A8 and TCF7L2 by quantitative RT-PCR in human pancreas (n = 50), colon (n = 195) and liver (n = 50). Tissue samples were genotyped for single nucleotide polymorphisms (SNPs) associated with type 2 diabetes. The effects of age, height, weight, tissue and SNP on RNA expression were tested by linear modelling.
RESULTS:
Expression of all genes exhibited tissue bias. Immunohistochemistry confirmed the findings for HHEX, IDE and SLC30A8, which showed strongest tissue-specific mRNA expression bias. Neither age, height nor weight were associated with gene expression. We found no evidence that type 2 diabetes-associated SNPs affect neighbouring gene expression (cis-expression quantitative trait loci) in colon, pancreas and liver.
CONCLUSIONS/INTERPRETATION:
This study provides new evidence that tissue-type, but not age, height, weight or SNPs in or near candidate genes associated with increased risk of type 2 diabetes are strong contributors to differential gene expression in the genes and tissues examined.

0 Bookmarks
 · 
73 Views

Full-text (2 Sources)

Download
27 Downloads
Available from
May 31, 2014