Association of CTLA-4 gene polymorphisms -318C/T and +49A/G and Hashimoto's thyroidits in Zahedan, Iran

Narooie‑Nejad,Mehrnaz; Taji,Omid; Kordi Tamandani,Dor Mohammad; Kaykhaei,Mahmoud   Ali

doi:10.3892/br.2016.813

Association of CTLA-4 gene polymorphisms -318C/T and +49A/G and Hashimoto's thyroidits in Zahedan, Iran

Authors:
- Mehrnaz Narooie‑Nejad
- Omid Taji
- Dor Mohammad Kordi Tamandani
- Mahmoud Ali Kaykhaei
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Affiliations: Genetics of Non‑Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Sistan and Baluchestan 9816743463, Iran, Department of Biology, University of Sistan and Baluchestan, Zahedan, Sistan and Baluchestan 98155-987, Iran
Published online on: November 17, 2016 https://doi.org/10.3892/br.2016.813
Pages: 108-112

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Abstract

Hashimoto's thyroiditis (HT) is a chronic inflammation of the thyroid gland and is known as the most common autoimmune disease. Development of autoimmune destruction of thyroid cells is a multi‑step process involving convergence of genetic and environmental factors. Cytotoxic T-lymphocyte antigen‑4 (CTLA-4) has an important role in homeostasis and negative regulation of immune responses, and is therefore considered to be a key element in the development of autoimmune diseases. The present study evaluated the association of the CTLA-4 gene polymorphisms 318C/T (rs5742909) and +49A/G (rs231775) with HT in an Iranian population (including 82 patients with HT and 104 healthy controls who were referred for routine premarital blood screenings). Genotyping was performed using the tetra‑primer amplification refractory mutation system polymerase chain reaction technique. No significant differences were observed in genotype and allele frequencies in the single nucleotide polymorphisms (SNPs) between cases and controls. In the cases as well as in the controls, the TT genotype in the -318C/T polymorphism was absent and the predominant genotype was CC, while the predominant genotype for the +49A/G SNP was AA. As only few studies in this field have assessed Iranian and even Middle Eastern populations, additional studies with a higher number of samples are recommended to further assess the impact of ‑318C/T (rs5742909) and +49A/G (rs231775) polymorphisms of CTLA-4 on HT.

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1	Kinney FJ and Herrmann RE: Increasing occurrence of thyroiditis in the Rocky Mountain area. Rocky Mt Med J. 59:35–37, passim. 1962.
2	Jacobson DL, Gange SJ, Rose NR and Graham NM: Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol. 84:223–243. 1997. View Article : Google Scholar : PubMed/NCBI
3	McLeod DS and Cooper DS: The incidence and prevalence of thyroid autoimmunity. Endocrine. 42:252–265. 2012. View Article : Google Scholar : PubMed/NCBI
4	Delemer B, Aubert JP, Nys P, Landron F and Bouée S: An observational study of the initial management of hypothyroidism in France: The ORCHIDÉE study. Eur J Endocrinol. 167:817–823. 2012. View Article : Google Scholar : PubMed/NCBI
5	Golden SH, Robinson KA, Saldanha I, Anton B and Ladenson PW: Clinical review: Prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive review. J Clin Endocrinol Metab. 94:1853–1878. 2009. View Article : Google Scholar : PubMed/NCBI
6	Chistiakov DA: Immunogenetics of Hashimoto's thyroiditis. J Autoimmune Dis. 2:12005. View Article : Google Scholar : PubMed/NCBI
7	Chistiakov DA and Turakulov RI: CTLA-4 and its role in autoimmune thyroid disease. J Mol Endocrinol. 31:21–36. 2003. View Article : Google Scholar : PubMed/NCBI
8	Caturegli P, De Remigis A, Chuang K, Dembele M, Iwama A and Iwama S: Hashimoto's thyroiditis: Celebrating the centennial through the lens of the Johns Hopkins hospital surgical pathology records. Thyroid. 23:142–150. 2013. View Article : Google Scholar : PubMed/NCBI
9	De Luca F, Santucci S, Corica D, Pitrolo E, Romeo M and Aversa T: Hashimoto's thyroiditis in childhood: Presentation modes and evolution over time. Ital J Pediatr. 39:82013. View Article : Google Scholar : PubMed/NCBI
10	Li Y, Bai Y, Liu Z, Ozaki T, Taniguchi E, Mori I, Nagayama K, Nakamura H and Kakudo K: Immunohistochemistry of IgG4 can help subclassify Hashimoto's autoimmune thyroiditis. Pathol Int. 59:636–641. 2009. View Article : Google Scholar : PubMed/NCBI
11	Stagnaro-Green A: Approach to the patient with postpartum thyroiditis. J Clin Endocrinol Metab. 97:334–342. 2012. View Article : Google Scholar : PubMed/NCBI
12	Ahmed R, Al-Shaikh S and Akhtar M: Hashimoto thyroiditis: A century later. Adv Anat Pathol. 19:181–186. 2012. View Article : Google Scholar : PubMed/NCBI
13	Caturegli P, De Remigis A and Rose NR: Hashimoto thyroiditis: Clinical and diagnostic criteria. Autoimmun Rev. 13:391–397. 2014. View Article : Google Scholar : PubMed/NCBI
14	Marković S, Kostić G, Igrutinović Z and Vuletić B: Hashimoto's thyroiditis in children and adolescents. Srp Arh Celok Lek. 136:262–266. 2008.(In Serbian). View Article : Google Scholar : PubMed/NCBI
15	Zaletel K and Gaberšček S: Hashimoto's thyroiditis: From genes to the disease. Curr Genomics. 12:576–588. 2011. View Article : Google Scholar : PubMed/NCBI
16	Menconi F, Monti MC, Greenberg DA, Oashi T, Osman R, Davies TF, Ban Y, Jacobson EM, Concepcion ES, Li CW, et al: Molecular amino acid signatures in the MHC class II peptide-binding pocket predispose to autoimmune thyroiditis in humans and in mice. Proc Natl Acad Sci USA. 105:14034–14039. 2008. View Article : Google Scholar : PubMed/NCBI
17	Hiromatsu Y, Satoh H and Amino N: Hashimoto's thyroiditis: History and future outlook. Hormones (Athens). 12:12–18. 2013.PubMed/NCBI
18	Han S, Zhang S, Zhang W, Li R, Li Y, Wang Z, Xie Y and Mao Y: CTLA4 polymorphisms and ophthalmopathy in Graves' disease patients: Association study and meta-analysis. Hum Immunol. 67:618–626. 2006. View Article : Google Scholar : PubMed/NCBI
19	Wang X-Y, Zuo D, Sarkar D and Fisher PB: Blockade of cytotoxic T-lymphocyte antigen-4 as a new therapeutic approach for advanced melanoma. Expert Opin Pharmacother. 12:2695–2706. 2011. View Article : Google Scholar : PubMed/NCBI
20	Walker LS and Sansom DM: The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses. Nat Rev Immunol. 11:852–863. 2011. View Article : Google Scholar : PubMed/NCBI
21	Narooie-Nejad M, Moossavi M, Torkamanzehi A and Moghtaderi A: Positive association of vitamin D Receptor gene variations with multiple sclerosis in South East Iranian population. BioMed Res Int. 2015:4275192015.PubMed/NCBI
22	Anjos S, Nguyen A, Ounissi-Benkalha H, Tessier MC and Polychronakos C: A common autoimmunity predisposing signal peptide variant of the cytotoxic T-lymphocyte antigen 4 results in inefficient glycosylation of the susceptibility allele. J Biol Chem. 277:46478–46486. 2002. View Article : Google Scholar : PubMed/NCBI
23	Kouki T, Sawai Y, Gardine CA, Fisfalen ME, Alegre ML and DeGroot LJ: CTLA-4 gene polymorphism at position 49 in exon 1 reduces the inhibitory function of CTLA-4 and contributes to the pathogenesis of Graves' disease. J Immunol. 165:6606–6611. 2000. View Article : Google Scholar : PubMed/NCBI
24	Qiu H, Tang W, Yin P, Cheng F and Wang L: Cytotoxic T-lymphocyte associated antigen 4 polymorphism and Hashimoto's thyroiditis susceptibility: A meta-analysis. Endocrine. 45:198–205. 2014. View Article : Google Scholar : PubMed/NCBI
25	Ji R, Feng Y and Zhan WW: Updated analysis of studies on the cytotoxic T-lymphocyte-associated antigen-4 gene A49G polymorphism and Hashimoto's thyroiditis risk. Genet Mol Res. 12:1421–1430. 2013. View Article : Google Scholar : PubMed/NCBI
26	Ahmadi S, Rostamzadeh J, Khosravi D, Shariati P and Shakiba N: Association of CTLA-4 gene 49A/G polymorphism with the incidence of type 1 diabetes mellitus in the Iranian Kurdish population. Pak J Biol Sci. 16:1929–1935. 2013. View Article : Google Scholar : PubMed/NCBI
27	Tang MJ and Zhou ZB: Association of the CTLA-4 +49A/G polymorphism with rheumatoid arthritis in Chinese Han population. Mol Biol Rep. 40:2627–2631. 2013. View Article : Google Scholar : PubMed/NCBI
28	Mora B, Bonamico M, Indovina P, Megiorni F, Ferri M, Carbone MC, Cipolletta E and Mazzilli MC: CTLA-4 +49 A/G dimorphism in Italian patients with celiac disease. Hum Immunol. 64:297–301. 2003. View Article : Google Scholar : PubMed/NCBI
29	Petrone A, Giorgi G, Mesturino CA, Capizzi M, Cascino I, Nistico L, Osborn J, Di Mario U and Buzzetti R: Association of DRB104-DQB10301 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. 2001. View Article : Google Scholar : PubMed/NCBI
30	Farra C, Awwad J, Fadlallah A, Sebaly G, Hage G, Souaid M, Ashkar H, Medlej R, Gannageh MH and Halaby G: Genetics of autoimmune thyroid disease in the Lebanese population. J Community Genet. 3:259–264. 2012. View Article : Google Scholar : PubMed/NCBI
31	Andreevskiĭ TV, Sudomoina MA, Gusev EI, Boĭko AN, Alekseenkov AD and Favorova OO: Polymorphism A/G in position +49 of CTLA4 exon 1 in multiple sclerosis in Russians. Mol Biol (Mosk). 36:643–648. 2002.(In Russian). PubMed/NCBI
32	Knight AK, Serrano D, Tomer Y and Cunningham-Rundles C: CTLA-4 gene exon-1 +49 A/G polymorphism: Lack of association with autoimmune disease in patients with common variable immune deficiency. J Clin Immunol. 27:95–100. 2007. View Article : Google Scholar : PubMed/NCBI
33	van Gerven NM, de Boer YS, Zwiers A, van Hoek B, van Erpecum KJ, Beuers U, van Buuren HR, Drenth JP, den Ouden JW, Verdonk RC, et al: Dutch Autoimmune Hepatitis Study group: Cytotoxic T lymphocyte antigen-4 +49A/G polymorphism does not affect susceptibility to autoimmune hepatitis. Liver Int. 33:1039–1043. 2013. View Article : Google Scholar : PubMed/NCBI
34	Monne M, Piras G, Palmas A, Arru L, Murineddu M, Latte G, Noli A and Gabbas A: Cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene polymorphism and susceptibility to non-Hodgkin's lymphoma. Am J Hematol. 76:14–18. 2004. View Article : Google Scholar : PubMed/NCBI
35	Ghaderi A: CTLA4 gene variants in autoimmunity and cancer: A comparative review. Iran J Immunol. 8:127–149. 2011.PubMed/NCBI
36	Balbi G, Ferrera F, Rizzi M, Piccioli P, Morabito A, Cardamone L, Ghio M, Palmisano GL, Carrara P, Pedemonte S, et al: Association of −318 C/T and +49 A/G cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms with a clinical subset of Italian patients with systemic sclerosis. Clin Exp Immunol. 149:40–47. 2007. View Article : Google Scholar : PubMed/NCBI
37	Muñoz-Valle JF, Valle Y, Padilla-Gutiérrez JR, Parra-Rojas I, Rangel-Villalobos H, del Mercado M Vázquez, Ledezma-Lozano IY, Villafan-Bernal JR, Armendáriz-Borunda J and Pereira-Suárez AL: The +49A>G CTLA-4 polymorphism is associated with rheumatoid arthritis in Mexican population. Clin Chim Acta. 411:725–728. 2010. View Article : Google Scholar : PubMed/NCBI
38	Yeşilkaya E, Koç A, Bideci A, Camurdan O, Boyraz M, Erkal O, Ergun MA and Cinaz P: CTLA4 gene polymorphisms in children and adolescents with autoimmune thyroid diseases. Genet Test. 12:461–464. 2008. View Article : Google Scholar : PubMed/NCBI
39	Pastuszak-Lewandoska D, Domańska D, Rudzińska M, Bossowski A, Kucharska A, Sewerynek E, Czarnecka K, Migdalska-Sęk M and Czarnocka B: 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. Acta Biochim Pol. 60:641–646. 2013.PubMed/NCBI
40	Heidari A, Daloii MR Noori, Keramatipour M, Rashikinezhad A, Sahmani AA and Amirzargar AA: CTLA-4 gene polymorphisms (−318C/T, +49A/G, +6230A/G) in Iranian patients with multiple sclerosis. Iran J Allergy Asthma Immunol. 9:219–223. 2010.PubMed/NCBI
41	Han SZ, Zhang SH, Li R, Zhang WY and Li Y: The common −318C/T polymorphism in the promoter region of CTLA4 gene is associated with reduced risk of ophthalmopathy in Chinese Graves' patients. Int J Immunogenet. 33:281–287. 2006. View Article : Google Scholar : PubMed/NCBI