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

Authors

  • José Manuel Fernández-Real,

    1. Section of Diabetes, Endocrinology and Nutrition, Institut d’Investigació Biomédica de Girona and CIBER Fisiopatología de la Obesidad y Nutrición (CB06/03/010), Girona, Spain
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  • Josep Maria Mercader,

    1. Barcelona Supercomputing Center, Jordi Girona, and CIBER Fisiopatologia Obesidad y Nutricion (CIBEROBN), Barcelona, Spain
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  • Francisco José Ortega,

    1. Section of Diabetes, Endocrinology and Nutrition, Institut d’Investigació Biomédica de Girona and CIBER Fisiopatología de la Obesidad y Nutrición (CB06/03/010), Girona, Spain
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  • Jose Maria Moreno-Navarrete,

    1. Section of Diabetes, Endocrinology and Nutrition, Institut d’Investigació Biomédica de Girona and CIBER Fisiopatología de la Obesidad y Nutrición (CB06/03/010), Girona, Spain
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  • Pedro López-Romero,

    1. Genomics Unit, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain
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  • Wifredo Ricart

    1. Section of Diabetes, Endocrinology and Nutrition, Institut d’Investigació Biomédica de Girona and CIBER Fisiopatología de la Obesidad y Nutrición (CB06/03/010), Girona, Spain
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José Manuel Fernández-Real, MD, PhD, Unit of Diabetes, Endocrinology and Nutrition. Hospital de Girona ‘Dr Josep Trueta’, Ctra. França s/n, 17007 Girona, Spain. Tel.: 34-972-94 02 00; fax: 34-972-227 443; e-mail: jmfernandezreal.girona.ics@gencat.cat

Abstract

Eur J Clin Invest 2010; 40 (7): 600–607

Abstract

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.

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