Association between polymorphic markers in candidate genes and the risk of manifestationof endocrine ophthalmopathy in patients with Graves’ disease


Cite item

Full Text

Abstract

Aim. To analyze the association between the polymorphic markers in CTLA4, TNF, IL10 and IL16 genes and the risk of manifestation of endocrine ophthalmopathy (EO) in patients with Graves’ disease (GD). Materials and methods. Case-control study included 248 patients with GD. Using polymerase chain reaction we studied the distribution of alleles and genotypes of polymorphic markers such as A60G (rs3087243) in CTLA4 gene, G(-308)A (rs1800629) in TNF gene, G(-1082)A (rs1800896) in IL10 gene, T3249C (rs4778641) in IL16 gene among 141 patients with Graves’ disease and EO and 107 patients with GD without EO. Results and discussion. The frequencies of A alleles and the AA genotypes were significantly increased and the frequencies of G alleles and the GG genotype polymorphic markers rs3087243 of CTLA4 gene and rs1800896 of IL10 gene, as well as the GG genotype polymorphic marker rs1800629 of TNF gene were reduced in patients with GD and EO. The polymorphism in CTLA4 gene was also associated with the activity and the severity of EO. The comparative analysis of the allele and genotype frequency distribution of polymorphic markers of IL16 gene did not show the significant difference. Conclusion. The risk of manifestation and the development of EO in patients with Graves’ disease can be caused by not only environmental, but also genetic risk factors.

About the authors

N A Petunina

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

д.м.н., проф., зав. каф. эндокринологии Первого МГМУ им. И.М. Сеченова Moscow, Russia

N S Martirosian

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: narinarine@list.ru
к.м.н., ассистент каф. эндокринологии Первого МГМУ им. И.М. Сеченова Минздрава России Moscow, Russia

L V Trukhina

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

к.м.н., доц. каф. эндокринологии Первого МГМУ им. И.М. Сеченова Moscow, Russia

S V Saakyan

Moscow Helmholtz Research Institute of Eye Diseases

д.м.н., проф., руководитель отд. офтальмоонкологии и радиологии МНИИ ГБ им. Гельмгольца Moscow, Russia

O G Panteleeva

Moscow Helmholtz Research Institute of Eye Diseases

д.м.н., в.н.с. отд. офтальмоонкологии и радиологии МНИИ ГБ им. Гельмгольца Moscow, Russia

A M Burdennyy

N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences

к.б.н., н.с. ИБХФ РАН Moscow, Russia

V V Nosikov

N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences

д.б.н., зав. лаб. постгеномных молекулярно-генетических исследований ИБХФ РАН Moscow, Russia

References

  1. Zhu W, Liu N, Zhao Y, Jia H, Cui B, Ning G. Association analysis of polymorphisms in IL-3, IL-4, IL-5, IL-9, and IL-13 with Graves’ disease. J Endocrinol Invest. 2010;33:751-755. doi: 10.1155/2014/537969
  2. Niyazoglu M, Baykara O, Koc A, Aydoğdu P, Onaran I, Dellal F.D, Tasan E, Sultuybek G.K. Association of PARP-1, NF-κB, NF-κBIA and IL-6, IL-1β and TNF-α with Graves Disease and Graves Ophthalmopathy. Gene. 2014 Sep 1;547(2):226-232. doi: 10.1016/j.humimm.2004.02.033
  3. Liu N, Li X, Liu C, Zhao Y, Cui B, Ning G. The association of interleukin-1alpha and interleukin-1beta polymorphisms with the risk of Graves’ disease in a case - control study and meta - analysis. Hum Immunol. 2010;71:39740. doi: 10.1038/eye.2009.244
  4. Du P, Ma X, Wang C. Associations of CTLA4 Gene Polymorphisms with Graves’ Ophthalmopathy: A Meta-Analysis. Int J Genomics. 2014;2014:537969. doi: 10.1167/iovs.09-4965
  5. Bednarczuk T, Hiromatsu Y, Seki N, Ploski R, Fukutani T, Kurylowicz A, Jazdzewski K, Chojnowski K, Itoh K, Nauman J. Association of tumor necrosis factor and human leukocyte antigen DRB1 alleles with Graves’ ophthalmopathy. Hum Immunol. 2004;65:632-639. doi: 10.1186/1423-0127-19-97
  6. Anvari M, Khalilzadeh O, Esteghamati A, Esfahani S.A, Rashidi A, Etemadi A, Mahmoudi M, Amirzargar A.A. Genetic susceptibility to Graves’ ophthalmopathy: the role of polymorphisms in proinflammatory cytokine genes. Eye (Lond). 2010 Jun;24(6):1058-1063. doi: 10.3109/13816810.2010.515648
  7. Liu Y.H, Chen R.H, Wu H.H, Liao W.L, Chen W.C, Tsai Y, Tsai C.H, Wan L, Tsai F.J. Association of interleukin-1 beta (IL1B) polymorphisms with Graves' ophthalmopathy in Taiwan Chinese patients. Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6238-6246. doi: 10.1007/BF03346682
  8. Liu Y.H, Chen C.C, Liao L.L, Wan L, Tsai C.H, Tsai F.J. Association of IL12B polymorphisms with susceptibility to Graves ophthalmopathy in a Taiwan Chinese population. J Biomed Sci. 2012 Nov 19;19:97. doi: 10.1016/j.gene.2014.06.038
  9. Khalilzadeh O, Anvari M, Esteghamati A, Momen-Heravi F, Rashidi A, Amiri H.M, Tahvildari M, Mahmoudi M, Amirzargar A. Genetic susceptibility to Graves’ ophthalmopathy: The role of polymorphisms in anti - inflammatory cytokine genes. Ophthalmic Genet. 2010;31:215-220. doi: 10.1016/j.humimm.2010.01.023
  10. Серкин Д.М., Серебрякова О.В., Серкин М.А., Харинцева С.В., Страмбовская Н.Н., Дагбаева С.Д. Роль полиморфизмов PRO12ALA и C1431T PPARγ в развитии эндокринной офтальмопатии. Клиническая и экспериментальная тиреоидология. 2013;9(3)51-55. doi: 10.14341/ ket20139351-55
  11. Vaidya B, Imrie H, Perros P, Dickinson J, Mc Carthy M.I, Kendall-Taylor P, Pearce S.H. Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism confers susceptibility to thyroid associated orbitopathy. Lancet. 1999;354:743-744. doi: 10.1016/S0140-6736(99)01465-8
  12. Zhang Q, Yang Y.M, Lv X.Y. 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. 2006 Nov;7(11):887-891. doi: 10.1631/jzus.2006.B0887
  13. Esteghamati A, Khalilzadeh O, Mobarra Z, Anvari M, Tahvildari M, Amiri H.M, Rashidi A, Solgi G, Parivar K, Nikbin B, Amirzargar A. Association of CTLA-4 gene polymorphism with Graves’ disease and ophthalmopathy in Iranian patients. Eur J Intern Med. 2009 Jul;20(4):424-428. doi: 10.1631/jzus.2006.B0887
  14. Han S, Zhang S, Zhang W, Li R, Li Y, Wang Z, Xie Y, Mao Y. CTLA4 polymorphisms and ophthalmopathy in Graves’ disease patients: association study and meta - analysis. Hum Immunol. 2006;67:618626. doi: 10.1016/j.humimm.2006.05.003
  15. Zaletel K, Krhin B, Gaberscek S, Pirnat E, Hojker S. 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. 2002;12:373-376. doi: 10.1089/105072502760043431
  16. Yan S.L, Wang Y.X. The relevance of tumor necrosis factor alpha gene-863C/A polymorphism with thyroid - associated ophthalmopathy. Zhonghua Yan Ke Za Zhi. 2005;41:786-790. doi: 10.3760/j:issn:0412-4081.2005.09.005

Copyright (c) 2018 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 
 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies