Transferrin receptor-1 gene polymorphisms are associated with type 2 diabetes
Version of Record online: 23 MAY 2010
© 2010 The Authors. Journal Compilation © 2010 Stichting European Society for Clinical Investigation Journal Foundation
European Journal of Clinical Investigation
Volume 40, Issue 7, pages 600–607, July 2010
How to Cite
Fernández-Real, J. M., Mercader, J. M., Ortega, F. J., Moreno-Navarrete, J. M., López-Romero, P. and Ricart, W. (2010), Transferrin receptor-1 gene polymorphisms are associated with type 2 diabetes. European Journal of Clinical Investigation, 40: 600–607. doi: 10.1111/j.1365-2362.2010.02306.x
- Issue online: 9 JUN 2010
- Version of Record online: 23 MAY 2010
- Received 21 September 2009; accepted 8 April 2010
- genetic polymorphism;
- insulin resistance;
- transferrin receptor;
- type 2 diabetes
Eur J Clin Invest 2010; 40 (7): 600–607
Background Iron is involved in oxidative stress and type 2 diabetes (T2D). Transferrin receptor (TFRC) constitutes the major receptor by which most cells take up iron. The aim of this study was to evaluate whether TFRC gene polymorphisms are associated with T2D.
Materials and methods We evaluated TFRC gene polymorphism (rs3817672, 210AG, S142G) in a sample of T2D patients and nondiabetic controls (n = 722), and 39 SNPs within the TFRC genomic region analysed by the Welcome Trust Case Control Consortium (WTCCC) (1921 T2D subjects and 3000 controls). In a subset of subjects, glucose tolerance and insulin sensitivity were also studied.
Results The frequency of the G allele at the position 210 of the TFRC gene was significantly higher in T2D patients. Both GG and GA genotypes had a 69% (P < 0·01) greater risk of developing T2D estimated under a dominant model. The increased prevalence of the G allele run in parallel to increased sex-adjusted log-serum ferritin and slightly increased soluble transferrin receptor among patients with T2D. Furthermore, post-load glucose and insulin sensitivity were significantly associated with circulating soluble transferrin receptor, and insulin sensitivity was significantly associated with serum ferritin among G allele carriers, (r = −0·33, P = 0·001) but not in AA homozygotes. Sixteen other TFRC SNPs were also associated to T2D according to the Welcome Trust Case Control Consortium data.
Conclusion TFRC gene variants are associated with T2D.