Polymorphisms in the TNFA and IL6 Genes Represent Risk Factors for Autoimmune Thyroid Disease

被引:33
作者
Duraes, Cecilia [1 ]
Moreira, Carla S. [1 ,2 ]
Alvelos, Ines [1 ]
Mendes, Adelia [1 ]
Santos, Liliana R. [2 ,3 ]
Machado, Jose Carlos [1 ,2 ]
Melo, Miguel [1 ,4 ,5 ]
Esteves, Cesar [6 ]
Neves, Celestino [2 ,6 ]
Sobrinho-Simoes, Manuel [1 ,2 ,7 ]
Soares, Paula [1 ,2 ,7 ]
机构
[1] Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, Oporto, Portugal
[2] Univ Porto, Fac Med, P-4100 Oporto, Portugal
[3] Univ Coimbra, Fac Med, Coimbra, Portugal
[4] Univ & Hosp Ctr Coimbra, Dept Diabet Endocrinol & Metab, Coimbra, Portugal
[5] Univ Coimbra, Fac Med, Unit Endocrinol, Coimbra, Portugal
[6] Hosp Sao Joao, Dept Endocrinol, Oporto, Portugal
[7] Univ Porto, Fac Med, Dept Pathol & Oncol, P-4100 Oporto, Portugal
来源
PLOS ONE | 2014年 / 9卷 / 08期
关键词
INTERLEUKIN-1 RECEPTOR ANTAGONIST; INTERFERON-GAMMA RECEPTOR; FACTOR-ALPHA PROMOTER; GRAVES-DISEASE; T-CELLS; CHINESE PATIENTS; IFN-GAMMA; ASSOCIATION; SUSCEPTIBILITY; OPHTHALMOPATHY;
D O I
10.1371/journal.pone.0105492
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 = 4.4x10(-5)) and log-additive (OR = 1.64, CI = 1.28-2.10, p-value = 8.2x10(-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 = 8.9x10(-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 = 7.0x10(-3)) and log-additive (OR = 1.69, CI = 1.17-2.44, p-value = 6.6x10(-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.
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页数:6
相关论文
共 59 条
[1]   Graves' disease and gene polymorphism of TNF-α, IL-2, IL-6, IL-12, and IFN-γ [J].
Anvari, Mehdi ;
Khalilzadeh, Omid ;
Esteghamati, Alireza ;
Momen-Heravi, Fatemeh ;
Mahmoudi, Mahdi ;
Esfahani, Shadi Abdar ;
Rashidi, Armin ;
Amirzargar, Aliakbar .
ENDOCRINE, 2010, 37 (02) :344-348
[2]   Expression of tumour necrosis factor-alpha (TNF-alpha) mRNA and protein in pathological thyroid tissue and carcinoma cell lines [J].
Aust, G ;
Heuer, M ;
Laue, S ;
Lehmann, I ;
Hofmann, A ;
Heldin, NE ;
Scherbaum, WA .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 1996, 105 (01) :148-154
[3]   Role of interaction between variants in the PPARG and interleukin-6 genes on obesity related metabolic risk factors [J].
Barbieri, M ;
Rizzo, MR ;
Papa, M ;
Acampora, R ;
De Angelis, L ;
Olivieri, F ;
Marchegiani, F ;
Franceschi, C ;
Paolisso, G .
EXPERIMENTAL GERONTOLOGY, 2005, 40 (07) :599-604
[4]   Association of G-174C polymorphism of the interleukin-6 gene promoter with Graves' ophthalmopathy [J].
Bednarczuk, T ;
Kurylowicz, A ;
Hiromatsu, Y ;
Kiljanski, J ;
Telichowska, A ;
Nauman, J .
AUTOIMMUNITY, 2004, 37 (03) :223-226
[5]   Linkage of large-vessel carotid atherosclerotic stroke to inflammatory genes via a systematic screen [J].
Belfer, Inna ;
Wu, Tianxia ;
Hipp, Heather ;
Walter, Joan ;
Scully, Michele ;
Nyquist, Paul A. ;
Bollettino, Antonella ;
Goldman, David ;
Max, Mitchell B. ;
DeGraba, Thomas J. .
INTERNATIONAL JOURNAL OF STROKE, 2010, 5 (03) :145-151
[6]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[7]   IL-6-174 C/G polymorphism in the gastroenteropancreatic neuroendocrine tumors (GEP-NETs) [J].
Berkovic, Maja Cigrovski ;
Jokic, Mladen ;
Marout, Jasminka ;
Radosevic, Senka ;
Zjacic-Rotkvic, Vanja ;
Kapitanovic, Sanja .
EXPERIMENTAL AND MOLECULAR PATHOLOGY, 2007, 83 (03) :474-479
[8]  
BIOQUE G, 1995, CLIN EXP IMMUNOL, V102, P379
[9]   Analysis of MHC genes in a Tunisian isolate with autoimmune thyroid diseases: implication of TNF-308 gene polymorphism [J].
Bougacha-Elleuch, N ;
Rebai, A ;
Mnif, M ;
Makni, H ;
Bellassouad, M ;
Jouida, J ;
Abid, M ;
Hammadi, A .
JOURNAL OF AUTOIMMUNITY, 2004, 23 (01) :75-80
[10]   The interferon gamma receptor 1 (IFNGR1)-56C/T gene polymorphism is associated with increased risk of early gastric carcinoma [J].
Canedo, P. ;
Corso, G. ;
Pereira, F. ;
Lunet, N. ;
Suriano, G. ;
Figueiredo, C. ;
Pedrazzani, C. ;
Moreira, H. ;
Barros, H. ;
Carneiro, F. ;
Seruca, R. ;
Roviello, F. ;
Machado, J. C. .
GUT, 2008, 57 (11) :1504-1508