Transferrin receptor-1 gene polymorphisms are associated with type 2 diabetes

Eur J Clin Invest. 2010 Jul;40(7):600-7. doi: 10.1111/j.1365-2362.2010.02306.x. Epub 2010 May 23.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Ferritins / blood*
  • Humans
  • Insulin Resistance / physiology
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Receptors, Transferrin / genetics*


  • Blood Glucose
  • Receptors, Transferrin
  • Ferritins