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2013 | 60 | 4 |

Tytuł artykułu

CTLA-4 polymorphisms (+49 A/G and -318 C/T) are important genetic determinants of AITD susceptibility and predisposition to high levels of thyroid autoantibodies in Polish children - preliminary study

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
Autoimmune thyroid diseases (AITDs), including Hashimoto' s thyroiditis (HT) and Graves' disease (GD), are related to environmental and genetic factors. We analyzed the association of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) gene two polymorphisms (+49 A/G, -318 C/T) with HT and GD development in Polish children, and correlated both polymorphisms with the production of thyroid autoantibodies (TPOAb and TgAb). The study involved 49 AITD patients (age 10-19) with HT (n=25) or GD (n=24) and 69 healthy controls. SNP genotyping was performed using genomic DNA and TaqMan® probes. The obtained results indicated that CTLA-4 +49 GG genotype was significantly more frequent in both HT and GD patients, whereas the AA genotype was more common in controls. CTLA-4-318 CT genotype was significantly more frequent in AITD, and the CC genotype more often occurred in controls. Significantly higher median TPOAb and TgAb values were associated with G allele in HT, and with T allele in GD patients. Concluding, both studied polymorphisms seem to be important genetic determinants of the risk of HT and GD, and appear to be associated with a predisposition to high levels of TAbs and clinical AITD. The obtained results give more information on the distribution of the CTLA-4 polymorphism in Polish AITD children, and further support the proposal that the CTLA-4 gene plays an important role in a TAb production.

Słowa kluczowe

Wydawca

-

Rocznik

Tom

60

Numer

4

Opis fizyczny

p.641-646,ref.

Twórcy

  • Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Lodz, Poland
autor
  • Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Lodz, Poland
autor
  • Department of Biochemistry & Molecular Biology, Medical Center of Postgraduate Education, Warsaw, Poland
autor
  • Department of Pediatrics, Endocrinology, Diabetology with Cardiology Division, Medical University, Bialystok, Bialystok, Poland
autor
  • Department of Pediatrics and Endocrinology, Medical University of Warsaw, Warsaw, Poland
autor
  • Department of Endocrine Disorders and Bone Metabolism, 1st Chair of Endocrinology, Medical University of Lodz, Lodz, Poland
autor
  • Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Lodz, Poland
  • Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Lodz, Poland
autor
  • Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Lodz, Poland

Bibliografia

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  • Bicek A, Zaletel K, Gaberscek S, Pirnat E, Krhin B, Stopar TG, Hojker S (2009) 49A/G and CT60 polymorphisms of the cytotoxic T-lymphocyte-associated antigen 4 gene associated with autoimmune thyroid disease. Hum Immunol 70: 820-824. 
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  • Chistiakov DA, Savost'anov KV, Turakulov RI, Efremov IA, Demurov LM (2006) Genetic analysis and functional evaluation of the C/T (-318) and A/G(-1661) polymorphisms of the CTLA-4 gene in patients affected with Graves' disease. Clin Immunol 118: 233-242.  
  • Chong KK, Chiang SW, Wong GW, Tam PO, Ng TK, Hu YJ, Yam GH, Lam DS, Pang CP (2008) Association of CTLA-4 and IL-13 gene polymorphisms with Graves' disease and ophthalmopathy in Chinese children. Invest Ophthalmol Vis Sci 49: 2409-2415.  
  • Kavvoura FK, Akamizu T, Awata T, Ban Y, Chistiakov DA, Frydecka I et al. (2007) Cytotoxic T-lymphocyte associated antigen 4 gene polymorphisms and autoimmune thyroid disease: a meta-analysis. J Clin Endocrinol Metab 92: 3162-3170.  
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  • Kouki T, Gardine CA, Yanagawa T, Degroot LJ (2002) Relation of three polymorphisms of the CTLA-4 gene in patients with Graves' disease. J Endocrinol Invest 25: 208-213.  
  • Kristiansen OP, Larsen ZM, Pociot F (2000) CTLA4 in autoimmune diseases - a general susceptibility gene to autoimmunity? Genes Immun 1: 170-184.  
  • Kucharska AM, Gorska E, Wasik M, Pyrzak B, Demkow U (2009) Expression of CD152 (CTLA-4) in children with autoimmune thyroiditis and +49 A/G polymorphism of exon 1 of the CTLA-4 gene. J Physiol Pharmacol 60: 77-80.  
  • Ligers A, Teleshova N, Masterman T, Huang WX, Hillert J (2001) CTLA-4 gene expression is influenced by promoter and exon 1 polymorphisms. Genes Immun 2: 145-152. 
  • Manzotti CN, Tipping H, Perry LC, Mead KI, Blair PJ, Zheng Y, Sansom DM (2002) Inhibition of human T cell proliferation by CTLA-4 utilizes CD80 and requires CD25+regulatory T cells. Eur J Immunol 32: 2888-2896.  
  • Namo Cury A, Longui CA, Kochi C, Calliari LE, Scalissi N, Salles JE, Neves Rocha M, Barbosa de Melo M, Rezende Melo M, Monte O (2008) Graves' disease in Brazilian children and adults: lack of genetic association with CTLA-4 +49A\>G polymorphism. Horm Res 70: 36-41.  
  • Park YJ, Chung HK, Park DJ, Kim WB, Kim SW, Koh JJ, Cho BY (2000) Polymorphism in the promoter and exon 1 of the cytotoxic T lymphocyte antigen-4 gene associated with autoimmune thyroid disease in Koreans. Thyroid 10: 453-459.  
  • Pastuszak-Lewandoska D, Sewerynek E, Domańska D, Gładyś A, Skrzypczak R, Brzeziańska E (2012) CTLA-4 gene polymorphisms and their influence on the predisposition to the autoimmune thyroid diseases (Graves' disease and Hashimoto's thyroiditis). Arch Med Sci 8: 415-421.  
  • Petrone A, Giorgi G, Mesturino CA, Capizzi M, Cascino I, Nistico L, Osborn J, Di Mario U, Buzzetti R (2001) Association of DRB1*04-DQB1*0301 haplotype and lack of association of two polymorphic sites at CTLA-4 gene with Hashimoto's thyroiditis in an Italian population. Thyroid 11: 171-175.  
  • Petrone A, Giorgi G, Galgani A, Alemanno I, Corsello SM, Signore A, Di Mario U, Nisticò L, Cascino I, Buzzetti R (2005) CT60 single nucleotide polymorphisms of the cytotoxic T-lymphocyte associated antigen-4 gene region is associated with Graves' disease in an Italian population. Thyroid 15: 232-238.  
  • Tomer Y, Greenberg DA, Barbesino G, Concepcion E, Davies TF (2001) CTLA-4 and not CD28 is a susceptibility gene for thyroid autoantibody production. J Clin Endocrinol Metab 86: 1687-1693. 
  • Ueda H, Howson JM, Esposito L, Heward J, Snook H, Chamberlain G, et al. (2003) Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 423: 506-511.  
  • Vaidya B, Oakes EJ, Imrie H, Dickinson AJ, Perros P, Kendall-Taylor P, Pearce SH (2003) CTLA4 gene and Graves' disease: association of Graves' disease with the CTLA4 exon 1 and intron 1 polymorphisms, but not with the promoter polymorphism. Clin Endocrinol (Oxf) 58: 732-735.  
  • Vieland VJ, Huang Y, Bartlett C, Davies TF, Tomer Y (2008) A multilocus model of the genetic architecture of autoimmune thyroid disorder, with clinical implications. Am J Hum Genet 82: 1349-1356.  
  • Wang XB, Zhao X, Giscombe R, Lefvert AK (2002) A CTLA-4 gene polymorphism at position -318 in the promoter region affects the expression of protein. Genes Immun 3: 233-234.  
  • Yang J, Qin Q, Yan N, Zhu YF, Li C, Yang XJ, Wang X, Pandey M, Hou P, Zhang JA (2012) CD40 C/T(-1) and CTLA-4 A/G(49) SNPs are associated with autoimmune thyroid diseases in the Chinese population. Endocrine 41: 111-115.  
  • Yeşilkaya E, Koç A, Bideci A, Camurdan O, Boyraz M, Erkal O, Ergun MA, Cinaz P (2008) CTLA4 Gene Polymorphisms in Children and Adolescents with Autoimmune Thyroid Diseases. Genet Test 12: 461-464.  
  • Yung E, Cheng PS, Fok TF, Wong GW (2002) CTLA-4 gene A-G polymorphism and childhood Graves' disease. Clin Endocrinol (Oxf) 56: 649-653.  
  • Zaletel K, Krhin B, Gaberscek S, Pirnat E, Hojker S (2002) The influence of the exon 1 polymorphism of the cytotoxic T lymphocyte antigen 4 gene on thyroid antibody production in patients with newly diagnosed Graves' disease. Thyroid 12: 373-376. 
  • Zaletel K, Krhin B, Gaberscek S, Hojker S (2006) Thyroid autoantibody production is influenced by exon 1 and promoter CTLA-4 polymorphisms in patients with Hashimoto's thyroiditis. Int J Immunogenet 33: 87-91.  
  • Zhang Q, Yang YM, Lv XY (2006) Association of Graves' disease and Graves' ophthalmopathy with the polymorphisms in promoter and exon 1 of cytotoxic T lymphocyte associated antigen-4 gene. J Zhejiang Univ Sci B 7: 887-891. 

Typ dokumentu

Bibliografia

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