Table of Contents Author Guidelines Submit a Manuscript
Journal of Diabetes Research
Volume 2015, Article ID 405371, 11 pages
Research Article

Associations of Haplotypes Upstream of IRS1 with Insulin Resistance, Type 2 Diabetes, Dyslipidemia, Preclinical Atherosclerosis, and Skeletal Muscle LOC646736 mRNA Levels

1Institute of Pharmacology and Toxicology, Paracelsus Medical University, 5020 Salzburg, Austria
2Department of Laboratory Medicine, Paracelsus Medical University, 5020 Salzburg, Austria
3Department of Geriatric Medicine, Paracelsus Medical University, 5020 Salzburg, Austria
4Department of Internal Medicine I, Paracelsus Medical University, 5020 Salzburg, Austria
5Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria
6Department of Internal Medicine, Krankenhaus Hallein, 5400 Hallein, Austria

Received 9 December 2014; Revised 22 March 2015; Accepted 30 April 2015

Academic Editor: Mitsuhiko Noda

Copyright © 2015 Selma M. Soyal et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The genomic region ~500 kb upstream of IRS1 has been implicated in insulin resistance, type 2 diabetes, adverse lipid profile, and cardiovascular risk. To gain further insight into this chromosomal region, we typed four SNPs in a cross-sectional cohort and subjects with type 2 diabetes recruited from the same geographic region. From 16 possible haplotypes, 6 haplotypes with frequencies >0.01 were observed. We identified one haplotype that was protective against insulin resistance (determined by HOMA-IR and fasting plasma insulin levels), type 2 diabetes, an adverse lipid profile, increased C-reactive protein, and asymptomatic atherosclerotic disease (assessed by intima media thickness of the common carotid arteries). BMI and total adipose tissue mass as well as visceral and subcutaneous adipose tissue mass did not differ between the reference and protective haplotypes. In 92 subjects, we observed an association of the protective haplotype with higher skeletal muscle mRNA levels of LOC646736, which is located in the same haplotype block as the informative SNPs and is mainly expressed in skeletal muscle, but only at very low levels in liver or adipose tissues. These data suggest a role for LOC646736 in human insulin resistance and warrant further studies on the functional effects of this locus.