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PLoS One. 2014 Aug 15;9(8):e105492. doi: 10.1371/journal.pone.0105492. eCollection 2014.

Polymorphisms in the TNFA and IL6 genes represent risk factors for autoimmune thyroid disease.

Author information

1
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
2
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Faculty of Medicine of the University of Porto, Porto, Portugal.
3
Faculty of Medicine of the University of Porto, Porto, Portugal; Faculty of Medicine of the University of Coimbra, Coimbra, Portugal.
4
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Department of Endocrinology, Diabetes and Metabolism, University and Hospital Center of Coimbra, Coimbra, Portugal; Unit of Endocrinology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
5
Department of Endocrinology, Hospital of S. João, Porto, Portugal.
6
Faculty of Medicine of the University of Porto, Porto, Portugal; Department of Endocrinology, Hospital of S. João, Porto, Portugal.
7
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Faculty of Medicine of the University of Porto, Porto, Portugal; Department of Pathology and Oncology, Faculty of Medicine of the University of Porto, Porto, Portugal.

Abstract

BACKGROUND:

Autoimmune thyroid disease (AITD) comprises diseases including Hashimoto's thyroiditis and Graves' disease, both characterized by reactivity to autoantigens causing, respectively, inflammatory destruction and autoimmune stimulation of the thyroid-stimulating hormone receptor. AITD is the most common thyroid disease and the leading form of autoimmune disease in women. Cytokines are key regulators of the immune and inflammatory responses; therefore, genetic variants at cytokine-encoding genes are potential risk factors for AITD.

METHODS:

Polymorphisms in the IL6-174 G/C (rs1800795), TNFA-308 G/A (rs1800629), IL1B-511 C/T (rs16944), and IFNGR1-56 T/C (rs2234711) genes were assessed in a case-control study comprising 420 Hashimoto's thyroiditis patients, 111 Graves' disease patients and 735 unrelated controls from Portugal. Genetic variants were discriminated by real-time PCR using TaqMan SNP genotyping assays.

RESULTS:

A significant association was found between the allele A in TNFA-308 G/A and Hashimoto's thyroiditis, both in the dominant (OR = 1.82, CI = 1.37-2.43, p-value = 4.4×10(-5)) and log-additive (OR = 1.64, CI = 1.28-2.10, p-value = 8.2×10(-5)) models. The allele C in IL6-174 G/C is also associated with Hashimoto's thyroiditis, however, only retained significance after multiple testing correction in the log-additive model (OR = 1.28, CI = 1.06-1.54, p-value = 8.9×10(-3)). The group with Graves' disease also registered a higher frequency of the allele A in TNFA-308 G/A compared with controls both in the dominant (OR = 1.85, CI = 1.19-2.87, p-value = 7.0×10(-3)) and log-additive (OR = 1.69, CI = 1.17-2.44, p-value = 6.6×10(-3)) models. The risk for Hashimoto's thyroiditis and Graves' disease increases with the number of risk alleles (OR for two risk alleles is, respectively, 2.27 and 2.59).

CONCLUSIONS:

This study reports significant associations of genetic variants in TNFA and IL6 with the risk for AITD, highlighting the relevance of polymorphisms in inflammation-related genes in the etiopathogenesis of AITD.

PMID:
25127106
PMCID:
PMC4134306
DOI:
10.1371/journal.pone.0105492
[Indexed for MEDLINE]
Free PMC Article

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