ometendoОжирение и метаболизмObesity and metabolism2071-87132306-5524Endocrinology Research Centre10.14341/omet13313ometendo-13313Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESNew potential genetic predictors of autoimmune adrenal insufficiencyTroshinaE. A.

Ekaterina Troshina, MD, PhD, Professor, Corresponding member 

Moscow

Troshina.Ekaterina@endocrincentr.ruNuralievaN.

Nurana Nuralieva, MD, PhD

11, Dm. Ulyanova street, 117292 Moscow

Nuralieva.Nurana@endocrincentr.ruYukinaM. Yu.

Marina Yukina, MD, PhD

Moscow

Yukina.Marina@endocrincentr.ruMeremyaninaE. A.

Meremyanina Ekaterina, MD, PhD

Moscow

ekaterina@meremianina.ruDyakovI. N.

Ilya Dyakov, PhD

Moscow

dyakov.ilya@gmail.comSvitichO. A.

Svitich Oksana, MD, PhD, Professor, Academician

Moscow

Russian Academy of ScienceRussian FederationEndocrinology Research CentreRussian FederationI. Mechnikov Research Institute for Vaccines and SeraRussian Federation202514022026224278284Copyright © Troshina E.A., Nuralieva N., Yukina M.Y., Meremyanina E.A., Dyakov I.N., Svitich O.A., 20262026Troshina E.A., Nuralieva N., Yukina M.Y., Meremyanina E.A., Dyakov I.N., Svitich O.A.Troshina E.A., Nuralieva N., Yukina M.Y., Meremyanina E.A., Dyakov I.N., Svitich O.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.omet-endojournals.ru/jour/article/view/13313

AIM search for new genetic predictors of autoimmune adrenal insufficiency (AAI).

MATERIALS AND METHODS

MATERIALS AND METHODS: In n=54 patients with AAI (isolated and as part of type 2 autoimmune polyglandular syndrome (APS-2; group 1)) and n=32 healthy individuals (group 2) we analyzed polymorphisms in IL28B (rs12979860, rs8099917), TLR9 (rs5743836, rs352140), TLR2 (rs5743708).

RESULTS

RESULTS: In group 1, compared with group 2, a predominance of CT genotype of rs12979860 polymorphism of IL28B (p=0.024), and T allele of rs5743836 polymorphism of TLR9 (p=0.044) was revealed. The allele C of rs5743836 polymorphism of TLR9 (p=0.044) was more common in group 2 than in group 1. With respect to other genotypes, alleles and haplotypes, no significant differences (or differences at the level of statistical trend) were found between groups 1 and 2.

CONCLUSION

CONCLUSION: Thus, it is possible that the CT genotype according to the polymorphic locus rs12979860 of the IL28B gene and the allele T of the rs5743836 polymorphism of the TLR9 gene are prognostic markers that increase the likelihood of developing AAI due to violation the peripheral immune tolerance (IT), whereas the allele C of the rs5743836 polymorphism of the TLR9 gene performs a protective role in this disease in the Russian population.

toll-like receptorsinterferon-lambda receptorAddison’s diseasepolymorphismsThis work was supported by research project 123021300096-3 “New genetic predictors (variants) of tumor and non-tumor endocrine diseases in adults, determined by whole-exome sequencing, including in nuclear families” (2023–2025).ReferencesYukina MYu, Nuralieva NF, Troshina EA. Adrenal insufficiency. Moscow: Medical Information Agency, 2020Yukina MYu, Nuralieva NF, Troshina EA. Adrenal insufficiency. Moscow: Medical Information Agency, 2020Yukina M, Erofeeva T, Nuralieva N, Andreeva T, Savvateeva E, Dudko N, Troshina E, Rogaev E, Melnichenko G. Novel Gene Mutations Regulating Immune Responses in Autoimmune Polyglandular Syndrome With an Atypical Course. Journal of the Endocrine Society. 2021;5(8):1–9. doi: https://doi.org/10.1210/jendso/bvab077Yukina M, Erofeeva T, Nuralieva N, Andreeva T, Savvateeva E, Dudko N, Troshina E, Rogaev E, Melnichenko G. Novel Gene Mutations Regulating Immune Responses in Autoimmune Polyglandular Syndrome With an Atypical Course. Journal of the Endocrine Society. 2021;5(8):1–9. doi: https://doi.org/10.1210/jendso/bvab077Kanczkowski W. Role of toll-like receptors and inflammation in adrenal gland insufficiency / W. Kanczkowski, K. Zacharowski, S.R. Bornstein // Neuroimmunomodulation. 2010; 17(3):180-183Kanczkowski W. Role of toll-like receptors and inflammation in adrenal gland insufficiency / W. Kanczkowski, K. Zacharowski, S.R. Bornstein // Neuroimmunomodulation. 2010; 17(3):180-183Hellesen A. The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison’s disease / A. Hellesen, K. Edvardsen, L. Breivik [et al.]. Clin Exp Immunol. 2014;176(3):351-362Hellesen A. The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison’s disease / A. Hellesen, K. Edvardsen, L. Breivik [et al.]. Clin Exp Immunol. 2014;176(3):351-362National Library of Medicine [Electronic resource]. Access mode: https://www.ncbi.nlm.nih.gov/gene/282617National Library of Medicine [Electronic resource]. Access mode: https://www.ncbi.nlm.nih.gov/gene/282617Filippi C. M. TLR2 signaling improves immunoregulation to prevent type 1 diabetes / C. M. Filippi, K. Ehrhardt, E. A. Estes [et al.]. Eur J Immunol. 2011;41(5):1399-1409Filippi C. M. TLR2 signaling improves immunoregulation to prevent type 1 diabetes / C. M. Filippi, K. Ehrhardt, E. A. Estes [et al.]. Eur J Immunol. 2011;41(5):1399-1409Gharbia OM. Toll-like receptor 5 and Toll-like receptor 9 single nucleotide polymorphisms and risk of systemic lupus erythematosus and nephritis in Egyptian patients / O.M. Gharbia, S.A. R Bassiouni, M.E.S Zaki [et al.]. Egyptian Rheumatology and Rehabilitation. 2021;48. ID 49Gharbia OM. Toll-like receptor 5 and Toll-like receptor 9 single nucleotide polymorphisms and risk of systemic lupus erythematosus and nephritis in Egyptian patients / O.M. Gharbia, S.A. R Bassiouni, M.E.S Zaki [et al.]. Egyptian Rheumatology and Rehabilitation. 2021;48. ID 49Zhang Y. Analysis of the association of polymorphisms rs5743708 in TLR2 and rs4986790 in TLR4 with atopic dermatitis risk / Y. Zhang, H.-C. Wang, C. Feng, M. Yan Immunol Invest. 2019;48(2):169-180Zhang Y. Analysis of the association of polymorphisms rs5743708 in TLR2 and rs4986790 in TLR4 with atopic dermatitis risk / Y. Zhang, H.-C. Wang, C. Feng, M. Yan Immunol Invest. 2019;48(2):169-180Gatselis NK. Programmed cell death-1 rs11568821 and interleukin28B rs12979860 polymorphisms in autoimmune hepatitis / N.K. Gatselis, K. Azariadis, A. Lyberopoulou, G.N. Dalekos. J Transl Autoimmun. 2021;4. ID 100126Gatselis NK. Programmed cell death-1 rs11568821 and interleukin28B rs12979860 polymorphisms in autoimmune hepatitis / N.K. Gatselis, K. Azariadis, A. Lyberopoulou, G.N. Dalekos. J Transl Autoimmun. 2021;4. ID 100126Chen J.-Y. Interferon-λ3/4 genetic variants and interferon-λ3 serum levels are biomarkers of lupus nephritis and disease activity in Taiwanese / J.-Y. Chen, C.-M. Wang, T.-D. Chen [et al.]. Arthritis Res Ther. 2018;20(1). ID 193Chen J.-Y. Interferon-λ3/4 genetic variants and interferon-λ3 serum levels are biomarkers of lupus nephritis and disease activity in Taiwanese / J.-Y. Chen, C.-M. Wang, T.-D. Chen [et al.]. Arthritis Res Ther. 2018;20(1). ID 193

The authors declare that there are no conflicts of interest present.