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Association of the polymorphous marker G6230A of the CTLA4 gene with type 1 diabetes mellitus in the patients of Russian descent

https://doi.org/10.14341/probl201258414-17

Abstract

The risk of devolvement of type 1 diabetes mellitus (DM1) remains a challenging problem because neither etiology of the disease nor its prognosis and genetic predisposition to this condition are clearly understood. The development of any autoimmune process starts from the disturbance of subtle molecular mechanisms involved in the regulation of the immune system. Therefore, the genes controlling the function of its major components are at the same time the potential candidate genes encoding for the predisposition to DM1. Their association with the disease was studied by means of comparative analysis of the frequency distribution of alleles and genotypes of the polymorphous rs3087243 (G6230A) marker of the CTLA4 gene encoding for antigen-4 of cytotoxic T-lymphocytes. The present study included 257 patients presenting with type 1 diabetes mellitus and 526 healthy subjects. Genotypes were identified by the "real time" amplification technique. The AA genotype was found to occur less frequently in the diabetic patients than in the control group (11.3% and 22.1% respectively). In contrast, the frequency of the GG genotype was higher in the patients with DM1 than in the healthy subjects (44.7% and 37.5% respectively). It is concluded that the polymorphous rs3087243 marker of the CTLA4 gene is significantly associated with the predisposition to the development of type 1 diabetes mellitus in the patients of Russian descent.

References

1. Дедов И.И., Шестакова М.В. Сахарный диабет. Руководство для врачей. М: Универсум Паблишинг 2003.

2. Pociot F., McDermott M.F. Genetics of type 1 diabetes mellitus. Genes Immun 2002; 3: 235-249.

3. Nisticò L., Buzzetti R., Pritchard L.E., Van der Auwera B., Giovannini C., Bosi E., Martinez L.M.T., Serrano R.M., Chow C.C., Cockram C.S. The CTLA-4 Gene Region of Chromosome 2q33 Is Linked to, and Associated with, Type 1 Diabetes. Human Mol Genet 1996; 5: 1075-1080.

4. Nisticò L., Cascino I., Buzzetti R., Pozzill P. CTLA-4 in Type 1 Diabetes Mellitus Landes Bioscience. Austin 2000.

5. Kavvoura F.K., Ioannidis J.P.A. CTLA-4 Gene Polymorphisms and Susceptibility to Type 1 Diabetes Mellitus: A HuGE Review and Meta-Analysis. Am J Epidemiol 2005; 162: 3-16.

6. Teft W.A., Kirchhof M.G., Madrenas J. A molecular perspective of CTLA-4 function. Ann Rev Immunol 2006; 24: 65-97.

7. Anjos S., Polychronakos C. Mechanisms of genetic susceptibility to type I diabetes: beyond HLA. Mol Genet Metab 2004; 81: 187-195.

8. Anjos S.M., Tessier M.-C., Polychronakos C. Association of the Cytotoxic T Lymphocyte-Associated Antigen 4 Gene with Type 1 Diabetes: Evidence for Independent Effects of Two Polymorphisms on the Same Haplotype Block. J Clin Endocrinol Metab 2004; 89: 6257-6265.

9. Anjos S., Nguyen A., Ounissi-Benkalha H., Tessier M.-C., 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 2002; 277: 46478-46486.

10. Wang X.B., Zhao X., Giscombe R., Lefvert A.K. A CTLA-4 gene polymorphism at position -318 in the promoter region affects the expression of protein. Genes Immun 2002; 3: 233-234.

11. Anjos S.M., Shao W., Marchand L., Polychronakos C. Allelic effects on gene regulation at the autoimmunity-predisposing CTLA4 locus: a re-evaluation of the 3[prime] +6230G>A polymorphism. Genes Immun 2005; 6: 305-311.

12. Awata T., Kawasaki E., Tanaka S., Ikegami H., Maruyama T., Shimada A., Nakanishi K., Kobayashi T., Iizuka H., Uga M. et al. Association of type 1 diabetes with two Loci on 12q13 and 16p13 and the influence coexisting thyroid autoimmunity in Japanese. J Clin Endocrinol Metab 2009; 94: 231-235.

13. Djilali-Saiah I., Larger E., Harfouch-Hammoud E., Timsit J., Clerc J., Bertin E., Assan R., Boitard C., Bach J.F., Caillat-Zucman S. No major role for the CTLA-4 gene in the association of autoimmune thyroid disease with IDDM. Diabetes 1998; 47: 125-127.

14. Golden B., Levin L., Ban Y., Concepcion E., Greenberg D.A., Tomer Y. Genetic analysis of families with autoimmune diabetes and thyroiditis: evidence for common and unique genes. J Clin Endocrinol Metab 2005; 90: 4904-4911.

15. Takara M., Komiya I., Kinjo Y., Tomoyose T., Yamashiro S., Akamine H., Masuda M., Takasu N. Association of CTLA-4 gene A/G polymorphism in Japanese type 1 diabetic patients with younger age of onset and autoimmune thyroid disease. Diabetes Care 2000; 23: 975-978.

16. Chistyakov D.A., Savost'anov K.V., Nosikov V.V. CTLA4 gene polymorphisms are associated with, and linked to, insulin-dependent diabetes mellitus in a Russian population. BMC Genetics 2001; 2: 1: 6.

17. Johns M.B., Paulus-Thomas J.E. Purification of human genomic DNA from whole blood using sodium perchlorate in place of phenol. Anal Biochem 1989; 180: 276-278.

18. Никитин А. Калькулятор для расчета статистики в исследованиях "случай-контроль". Available at: http://test.tapotili.ru/calculator_or.php 2009.


Review

For citations:


Kopylova O.I., Kuraeva T.L., Lavrikova E.I., Titovich E.V., Nikitin A.G., Smirnova G.E., Peterkova V.A., Dedov I.I., Nosikov V.V. Association of the polymorphous marker G6230A of the CTLA4 gene with type 1 diabetes mellitus in the patients of Russian descent. Problems of Endocrinology. 2012;58(4):14-17. https://doi.org/10.14341/probl201258414-17

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ISSN 0375-9660 (Print)
ISSN 2308-1430 (Online)