ASSOCIATION OF CTLA-4 AND PTPN-22 GENES POLYMORPHISMS WITH INCREASED RISK OF AUTOIMMUNE THYROIDITIS IN TATAR POPULATION
https://doi.org/10.15789/1563-0625-2010-1-2-103-114
Abstract
The aspects of autoimmune thyroiditis (AIT) remain quite actual, since many issues of etiology, pathogenesis, morphology, classification, diagnostics, therapy and prediction of this disorder are far from final solution. Since disturbances of fine molecular immune mechanisms underlie pathogenesis of either immune disorder, the genes coding its main components, are regarded as potential candidate genes predisposing for AIT, e.g., genes of surface antigen (CTLA-4) and protein tyrosine phosphatase non-receptor 22 (PTPN-22). We have performed genotyping of 298 Tatar women in Tatar Republic (Russia) with respect to age and biochemical parameters (control group, 137 persons; AIT group, 161 patients). The following gene polymorphisms were tested: +49 А/G, -318 С/Т, -1661 А/G of СТLA-4 gene, and 1858 С/Т polymorphism of PTPN-22 gene. Genotyрing was performed by PCR-RFLP method as described earlier. The data were analyzed using Chi-square test and 95% confidential interval (CI). The frequencies of CTLA-4 -1661 G allele and genotype A/G and +49 G/A G allele and genotype GG carriers were significantly higher in AIT patients than in controls (P = 0.04, OR 1.84, 95% CI 2.31-1.4; P = 0.001, OR 2,0 95% CI 1.62-2.31 respectively), with increased contents of serum antibodies to thyroglobulin (OR, 1.56, 95% CI 2.25-3.6; OR 1.12, 95% CI 1.9-2.75, respectively) and to thyroperoxidase (OR 1.3, 95% CI 1.5-4.1 for G/G genotype of +49 A/G polymorphism), independently of age (р < 0,05). We showed that the combinations of A/G, T/C and G/G genotypes of -1661 A/G, -318 T/C and +49 G/A polymorphisms is associated with increased risk of genetic predisposition to ITD in Tatar women (OR 7.87, 95% CI 2.03-3.25). A strong association was also observed between the increased level of antibodies to TPO (> 1000 ME/l) and GG genotype of +49 G/A polymorphism (OR 1.3, 95% CI 1.5-4.1) and antibodies to TG (> 100 ME/l) and genotypes A/G and G/G of CTLA-4 -1661 A/G and +49 G/A polymorphisms (OR 1.56, 95% CI 2.25-3.6; OR 1.12, 95% CI 1.9-2.75, respectively), independently of age. The genotypes -318 T/C and 1858 T/C of CTLA-4 and PTPN-22 genes, respectively, are not associated with AITD in Tatar women (p > 0.05). Our results suggest that polymorphisms of CTLA-4 and PTPN-22 genes may modify individual susceptibility to autoimmune thyroiditis in Tatar women.
About the Authors
E. M. Biktagirova
Казанский государственный университет им. В.И. Ульянова-Ленина,
биолого-почвенный факультет, кафедра биохимии, г. Казань
Russian Federation
Russian Federation
O. A. Kravtsova
Казанский государственный университет им. В.И. Ульянова-Ленина,
биолого-почвенный факультет, кафедра биохимии, г. Казань
Russian Federation
Russian Federation
L. I. Sattarova
Межрегиональный клинико-диагностический центр (МКДЦ), иммунологическая лаборатория, г. Казань
Russian Federation
Russian Federation
G. R. Vagapova
Межрегиональный клинико-диагностический центр (МКДЦ), иммунологическая лаборатория, г. Казань
Russian Federation
Russian Federation
References
1. Герасимов Г.А. Заболевания щитовидной железы // Здоровье. -1999 -№ 9 -С. 23-27.
2. Дедов И.И., Трошина Е.А., Александрова Г.Ф. Диагностика, лечение и профилактика узловых форм заболеваний щитовидной железы: Руководство для врачей. -M.: Хеми АГ, 1999. -С. 96-102.
3. Животский Л.А. Популяционная биометрия. -М.: Наука, 1991. -С.270.
4. Зефирова Г.С. Аутоиммунный треоидит и методы функциональной диагностики // Проблемы эндокринологии. -1999. -№ 12. - С. 16 -21.
5. Шилин Д.Е. Исследование антитиреоидных антител и тиреоглобулина в диагностике и контроле терапии заболеваний щитовидной железы // Проблемы эндокронологии. -1995. -Т. 41. -№ 3. -С.17-23.
6. Bowes J., Barton A. Recent advances in the genetics of RA susceptibility // Rheumatology. -2008. -Vol. 47. -Р. 399-402.
7. Charon A. Chung & Lindsey Criswell PTPN-22: Its role in SLE and autoimmunity // Autoimmunity. -2007. -Vol. 40, N 8. -Р. 582-590.
8. Chistyakov D. Complex associationanalysis of GD using a St of Polymorphic Markers // Molecular Genetics and Metabolism. -2000. -Vol. 70. -Р. 214-218.
9. Donner H., Braun J., Seidl C. et al. 17 polymorphism of the cytotoxic T Lymfocyte Antigen 4 Gene in Hashimoto’s Thyroiditis and Addisson’s disease // J. Of clinical endocrinilogy and matabolism. -1997. -Vol. 12. -Р. 4130-4133.
10. Elsie M.A., Hsuen W., Sabra M.M. A genome-Wide Scan for Autoimmune thyroiditis inthe Old Order Amish: Replication of Genetic Linkage on Chromosome 5q11.2-q14.3 // J. Of clinical endocrinilogy and matabolism. -2006. -Vol. 88. -P. 1292-1296.
11. Sakai K, Shirasawa S, Ishikawa N. Identification of susceptibility loci for autoimmune thyroid disease to 5q31-q33 and Hashimoto’s thyroiditis to 8q23-q24 by multipoint affected sib-pair linkage analysis in Japanese // Human molecular genetics. -2001. -Vol. 13. -P. 1379-1386.
12. Kotsa K. A., Weetman A.P. CTLA-4 gene polymorphism is associated with both Graves’ disease and Hashimoto’s thyroiditis // Clin. Endocrinol (Oxf). -1997 -Vol. 46 -P. 551-554.
13. Magistrelli G.A., Jeannin P., Herbault N. soluble form of CTLA-4 generated by alternative splicing is expressed by nonstimulated human T cells // Eur. J. Immunol. -1999. -Vol. 29, N 11. -P. 3596-3602.
14. Masaki Takara, Ichiro Komiya. Assotiation of CTLA-4 gene A/G polymorphism in Japanese type 1 diabetic patients with younger age of onset and AITD // Diabetes Care. -2000. -Vol. 23. -P. 975 -977.
15. Mathew C.G.P. The isolation of high molecular weight eukaryotic DNA. Methods in Molecular Biology // New York. -1984. -P. 31 -31.
16. Pauls D.L., Zakarija M. Complex Segregation analysis of antibodies to thyroid peroxidase in Old Amish families // Am. J. Med. Gen. -1993. -Vol. 47. -P. 375-379.
17. Jaume J.C., Guo J., Pauls D.L. Evidence for genetic transmission of thyroid peroxidase autoantibody epitopic «finger-prints» // J. Clin. Endocrinol Metab. -Vol. 84. -P. 1424-1431.
18. Velaga Mr., Wilson V. The codon 620 Tryptophan Allele of the Lymphoid tyrosine Phosphate (LYP) Gene is a major determinant of Graves’ Disesase // The Journal of Clinical Endocrinology & Matabolism. -2004. -Vol. 89, N 11. -Р. 5862-5865.
19. Wang L., Dalin Li, Zhenkun Fu. Association of CTLA-4 gene polymorphisms wiht sporadic breast cancer in Chinese Han population // BMC Cancer. -2007. -Vol. 7. -P. 173-184.
Review
For citations:
Biktagirova E.M., Kravtsova O.A., Sattarova L.I., Vagapova G.R. ASSOCIATION OF CTLA-4 AND PTPN-22 GENES POLYMORPHISMS WITH INCREASED RISK OF AUTOIMMUNE THYROIDITIS IN TATAR POPULATION. Medical Immunology (Russia). 2010;12(1-2):103-114. (In Russ.) https://doi.org/10.15789/1563-0625-2010-1-2-103-114
Views:
1104
Email this article 