Autoimmune thyroiditis (AIT) is a chronic inflammatory that involves hyperactivation of the immune system against the thyroid gland, recognizing it as "nonself”. The aim of this research was to identify the relationships between genetic polymorphism in CTLA4, TNF-α and PTPN22 genes and the manifestation of AIT and levels of antithyroglobulin antibody (anti-TG Ab) and thyroid peroxidase antibody (anti-TPO Ab). The study was conducted during 2014–2020 and included 64 men and 106 women aged between 18 and 64 years with AIT. The control group consisted of 65 people (26 men, 39 women, aged between 20 and 65 years) without any thyroid pathologies or other autoimmune diseases. For molecular genetic analysis, real-time quantitative RT-PCR was used with fluorescently labeled FAM probes on a detection system CFX96 (BioRad). The results demonstrated that patients with the GG genotype and the G allele of the +49A/G polymorphism in the CTLA4 gene have significantly higher titers of anti-TG Ab. High titers of anti-TG Ab were detected in 22.4% of patients with the GG genotype (p = 0.005, χ2 = 7.86, OR = 0.237, 95% CI = 0.088–0.635), and in 55.6% of patients with the G allele (p = 0.0012, χ2 = 10.43, OR = 0.360, 95%, СI = 0.192–0.674). At the same time, the A allele of the +49A/G polymorphism is significantly more common in patients with normal anti-TG Ab values—in 68.1% of individuals (p = 0.0012, χ2 = 10.43, OR= 2.78, 95%, CI = 1.484–5.207). The results of the study indicate the prognostic significance of the G allele and the GG genotype of the +49A/G polymorphism of the CTLA4 gene predicting the probability of occurrence of anti-TG and anti-TPO antibodies.
Citation: Rena Rahimova. Relationship between CTLA4, TNF-α and PTPN22 gene polymorphism and the serum levels of antithyroglobulin and antiperoxidase antibodies in autoimmune thyroiditis[J]. AIMS Medical Science, 2023, 10(1): 14-23. doi: 10.3934/medsci.2023002
Autoimmune thyroiditis (AIT) is a chronic inflammatory that involves hyperactivation of the immune system against the thyroid gland, recognizing it as "nonself”. The aim of this research was to identify the relationships between genetic polymorphism in CTLA4, TNF-α and PTPN22 genes and the manifestation of AIT and levels of antithyroglobulin antibody (anti-TG Ab) and thyroid peroxidase antibody (anti-TPO Ab). The study was conducted during 2014–2020 and included 64 men and 106 women aged between 18 and 64 years with AIT. The control group consisted of 65 people (26 men, 39 women, aged between 20 and 65 years) without any thyroid pathologies or other autoimmune diseases. For molecular genetic analysis, real-time quantitative RT-PCR was used with fluorescently labeled FAM probes on a detection system CFX96 (BioRad). The results demonstrated that patients with the GG genotype and the G allele of the +49A/G polymorphism in the CTLA4 gene have significantly higher titers of anti-TG Ab. High titers of anti-TG Ab were detected in 22.4% of patients with the GG genotype (p = 0.005, χ2 = 7.86, OR = 0.237, 95% CI = 0.088–0.635), and in 55.6% of patients with the G allele (p = 0.0012, χ2 = 10.43, OR = 0.360, 95%, СI = 0.192–0.674). At the same time, the A allele of the +49A/G polymorphism is significantly more common in patients with normal anti-TG Ab values—in 68.1% of individuals (p = 0.0012, χ2 = 10.43, OR= 2.78, 95%, CI = 1.484–5.207). The results of the study indicate the prognostic significance of the G allele and the GG genotype of the +49A/G polymorphism of the CTLA4 gene predicting the probability of occurrence of anti-TG and anti-TPO antibodies.
[1] | Ragusa F, Fallahi P, Elia G, et al. (2019) Hashimotos' thyroiditis: epidemiology, pathogenesis, clinic and therapy. Best Pract Res Clin Endocrinol Metab 33: 101367. https://doi.org/10.1016/j.beem.2019.101367 |
[2] | Weetman A (2020) Autoimmune thyroid disease. Endocrine 68: 258-260. https://doi.org/10.1007/s12020-020-02188-6 |
[3] | Rayman MP (2019) Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease. Proc Nutr Soc 78: 34-44. https://doi.org/10.1017/S0029665118001192 |
[4] | Antonelli A, Ferrari SM, Corrado A, et al. (2015) Autoimmune thyroid disorders. Autoimmun rev 14: 174-180. https://doi.org/10.1016/j.autrev.2014.10.016 |
[5] | Caturegli P, De Remigis A, Rose NR (2014) Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun rev 13: 391-397. https://doi.org/10.1016/j.autrev.2014.01.007 |
[6] | Rozhko VA (2019) The current state of the problem of autoimmune thyroiditis. Probl Health Ecol 60: 4-13. https://doi.org/10.51523/2708-6011.2019-16-2-1 (in Russian) |
[7] | Mattozzi S, Sabater L, Escudero D, et al. (2020) Hashimoto encephalopathy in the 21st century. Neurology 94: e217-e224. https://doi.org/10.1212/WNL.0000000000008785 |
[8] | Rahimova RR (2022) Autoimmune thyroiditis (review of literature). Russ Clin Lab Diagn 67: 286-291. https://doi.org/10.51620/0869-2084-2022-67-286-291 (in Russian) |
[9] | Ralli M, Angeletti D, Fiore M, et al. (2020) Hashimoto's thyroiditis: An update on pathogenic mechanisms, diagnostic protocols, therapeutic strategies, and potential malignant transformation. Autoimmun Rev 19: 102649. https://doi.org/10.1016/j.autrev.2020.102649 |
[10] | Steiner J, Schiltz K, Stoecker W, et al. (2020) Association of thyroid peroxidase antibodies with anti-neuronal surface antibodies in health, depression and schizophrenia—complementary linkage with somatic symptoms of major depression. Brain Behav Immun 90: 47-54. https://doi.org/10.1016/j.bbi.2020.07.039 |
[11] | Calcaterra V, Nappi RE, Regalbuto C, et al. (2020) Gender differences at the onset of autoimmune thyroid diseases in children and adolescents. Front Endocrinol 11: 229. https://doi.org/10.3389/fendo.2020.00229 |
[12] | Stasiak M, Lewiński A (2021) New aspects in the pathogenesis and management of subacute thyroiditis. Rev Endocr Metab Disord 22: 1027-1039. https://doi.org/10.1007/s11154-021-09648-y |
[13] | Stojković M (2022) Thyroid function disorders. Arch Pharm 72: 429-443. https://doi.org/10.5937/arhfarm72-39952 |
[14] | Komisarenko YI, Bobryk MI (2018) Vitamin D deficiency and immune disorders in combined endocrine pathology. Front Endocrinol 9: 600. https://doi.org/10.3389/fendo.2018.00600 |
[15] | Abazova ZK, Borukaeva IK (2019) Hypoxic therapy in the correction of neuroimmunoendocrine disorders in autoimmune thyroiditis. Med Acad J 19: 49-51. |
[16] | Rahimova RR (2022) On the issue of prediction of autoimmune thyroiditis. Azerbaijan Med J 2: 64-71. https://doi.org/10.34921/amj.2022.2.010 (in Russian) |
[17] | Kraus AU, Penna-Martinez M, Shoghi F, et al. (2019) HLA-DQB1 position 57 defines susceptibility to isolated and polyglandular autoimmunity in adults: interaction with gender. J Clin Endocrinol Metab 104: 1907-1916. https://doi.org/10.1210/jc.2018-01621 |
[18] | Bolotskaya LA, Tarlyun AA (2017) Pathophysiological significance of autoimmune markers for autoimmune thyroiditis onset in the middle OB residents. Vestnik SurGU Medicina 2: 31-35. Available from: https://surgumed.elpub.ru/jour/article/view/79?locale=en_US (in Russian) |
[19] | Guliyeva SR, Guliyeva FE, Abiyev HA, et al. (2022) Autoimmune thyroid diseases and genetic factors. World J Adv Res Rev 16: 690-696. https://doi.org/10.30574/wjarr.2022.16.1.1038 |
[20] | Gu LQ, Zhu W, Pan CM, et al. (2010) Tumor necrosis factor alpha (TNF-α) polymorphisms in Chinese patients with Graves' disease. Clin Biochem 43: 223-227. https://doi.org/10.1016/j.clinbiochem.2009.08.012 |
[21] | Stasiak M, Tymoniuk B, Michalak R, et al. (2020) Subacute thyroiditis is associated with HLA-B*18:01, -DRB1*01 and -C*04:01—the significance of the new molecular background. J Clin Med 9: 534. https://doi.org/10.3390/jcm9020534 |
[22] | Passali M, Josefsen K, Frederiksen JL, et al. (2020) Current evidence on the efficacy of gluten-free diets in multiple sclerosis, psoriasis, type 1 diabetes and autoimmune thyroid diseases. Nutrients 12: 2316. https://doi.org/10.3390/nu12082316 |
[23] | Vieira IH, Rodrigues D, Paiva I (2020) Vitamin D and autoimmune thyroid disease—cause, consequence, or a vicious cycle?. Nutrients 12: 2791. https://doi.org/10.3390/nu12092791 |
[24] | Wawrusiewicz-Kurylonek N, Koper-Lenkiewicz OM, Gościk J, et al. (2019) Association of PTPN22 polymorphism and its correlation with Graves' disease susceptibility in Polish adult population-A preliminary study. Mol Genet Genomic Med 7: e661. https://doi.org/10.1002/mgg3.661 |
[25] | Weetman A, DeGroot LJ (2016) Autoimmunity to the Thyroid Gland. [Updated 2016 Jan 14]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc. 2000–. Available from: https://www.ncbi.nlm.nih.gov/books/NBK285552/ |