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Analysis of thyroglobulin gene polymorphisms in patients with autoimmune thyroiditis

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Abstract

The autoimmune thyroid disease is a complex disorder caused by a combination of genetic susceptibility and environmental factors, which are believed to initiate the autoimmune response to thyroid antigens. Identification of the susceptibility genes has found that unique and diverse genetic factors are in association with Graves’ disease and autoimmune thyroiditis. The thyroglobulin gene is an identified thyroid-specific gene associated to autoimmune thyroid disease and, principally, with autoimmune thyroiditis. The aim of this work was to test for evidence of allelic association between autoimmune thyroiditis and thyroglobulin polymorphism markers. We studied six polymorphisms distributed throughout all the thyroglobulin gene: four microsatellites (Tgms1, Tgms2, TGrI29 and TGrI30), one insertion/deletion (Indel) polymorphism (IndelTG-IVS18) and one exonic single nucleotide polymorphism (SNP) (c.7589G>A) in 122 patients with autoimmune thyroiditis compared with 100 non-related normal subjects. No differences in allele and genotype distribution were observed between autoimmune thyroiditis cases and controls for Tgms1, Tgms2, TGrI30, IndelTG-IVS18 and c.7589G>A. However, when we analyzed the patients with the TGrI29 microsatellite we found a significant association between the 199-bp allele and AT (33.7% vs. 24.5% in control group) (P = 0.0372). In addition, a higher prevalence of the 201-bp allele has been observed in control subjects (47.5% vs. 38.1% in patients group), although not statistically significant (P = 0.0536). Our work shows the association between the thyroglobulin gene and autoimmune thyroiditis and reinforce that thyroglobulin is a thyroid-specific susceptibility gene for this disease.

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Abbreviations

AITD:

Autoimmune thyroid diseases

AT:

Autoimmune thyroiditis

GD:

Graves’ disease

TG:

Thyroglobulin

TPO:

Thyroid peroxidase

TSH-R:

Thyroid-stimulating hormone receptor

HLA:

Human leukocyte antigen

CTLA4:

Cytotoxic T lymphocyte-associated-4

SNP:

Single nucleotide polymorphism

Indel:

Insertion/deletion

SDS:

Sodium dodecyl sulphate

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Acknowledgements

M. Caputo is a research fellow of the University of Buenos Aires. C. M. Rivolta and H. M. Targovnik are established investigators of the CONICET and have been visiting professors in the Department of Medicine, University of Salamanca, Spain. This work was supported by grants in Spain from Fondo de Investigaciones Sanitarias (PI020309 to JMMG), Junta de Castilla y León (Biomedicina, 92/A/06 to JMMG), MCYT (PM99-0070 to RG-S) and Fundación MM (FMM 2005 to RG-S) and in Argentine from Universidad de Buenos Aires (B 057/2004 to HMT), CONICET (5360/2005 to CMR and HMT) and ANPCyT-FONCyT (05-21081/PICT 2004 to HMT). The authors are grateful to Nieves Mateos and Pilar Rodríguez for their excellent technical assistance.

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Authors and Affiliations

  1. Laboratorio de Biología Molecular, Cátedra de Genética y Biología Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, 1113, Buenos Aires, Argentina

    Mariela Caputo, Carina M. Rivolta & Héctor M. Targovnik

  2. Unidad de Medicina Molecular, Departamento de Medicina, Facultad de Medicina, Universidad de Salamanca, 37007, Salamanca, Spain

    Carina M. Rivolta, Rogelio González-Sarmiento & Héctor M. Targovnik

  3. Servicio de Endocrinología y Nutrición, Hospital Universitario de Salamanca, Universidad de Salamanca, 37007, Salamanca, Spain

    Teresa Mories, Juan J. Corrales & José M. Miralles-García

  4. Departamento de Estadística, Universidad de Salamanca, 37007, Salamanca, Spain

    Purificación Galindo

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  1. Mariela Caputo
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  2. Carina M. Rivolta
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  3. Teresa Mories
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  4. Juan J. Corrales
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  7. Héctor M. Targovnik
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  8. José M. Miralles-García
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Correspondence to José M. Miralles-García.

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Caputo, M., Rivolta, C.M., Mories, T. et al. Analysis of thyroglobulin gene polymorphisms in patients with autoimmune thyroiditis. Endocr 37, 389–395 (2010). https://doi.org/10.1007/s12020-010-9317-5

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