Polymorphisms in the TNFA and IL6 genes represent risk factors for autoimmune thyroid disease.
PLoS One
; 9(8): e105492, 2014.
Article
em En
| MEDLINE
| ID: mdl-25127106
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 (ORâ=â1.82, CIâ=â1.37-2.43, p-valueâ=â4.4×10(-5)) and log-additive (ORâ=â1.64, CIâ=â1.28-2.10, p-valueâ=â8.2×10(-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 (ORâ=â1.28, CIâ=â1.06-1.54, p-valueâ=â8.9×10(-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 (ORâ=â1.85, CIâ=â1.19-2.87, p-valueâ=â7.0×10(-3)) and log-additive (ORâ=â1.69, CIâ=â1.17-2.44, p-valueâ=â6.6×10(-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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Doença de Graves
/
Interleucina-6
/
Fator de Necrose Tumoral alfa
/
Doença de Hashimoto
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Portugal