Association between Human Leukocyte Antigen Alleles and Endocrine Disorders in a Cohort of 895 Patients from Russian Clinical Population

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Anton A. Buzdin^1,2,3,4, Polina A. Pugacheva^1,3, Daniil V. Luppov^1,3, Marianna A. Zolotovskaia^1,3,a*, Maxim I. Sorokin^1,2, Sergey A. Roumiantsev¹, Aleksandra G. Emelyanova^1,3, Olga O. Golounina¹, Arseniya O. Alexeeva^1,3, Anna A. Emelianova^1,2, Aleksey L. Novoselov¹, Anna Y. Khristichenko¹, Alina V. Matrosova¹, Sergey V. Popov¹, Evgeniya V. Plaksina¹, Vasiliy M. Petrov¹, Anastasia R. Guselnikova¹, Zhanna E. Belaya¹, Mary Woroncow⁵, Galina A. Melnichenko¹, Ekaterina A. Troshina¹, Marina V. Shestakova¹, Olga B. Bezlepkina¹, Valentina A. Peterkova¹, Natalia G. Mokrysheva¹, Vladimir P. Chekhonin¹, and Ivan I. Dedov¹

¹Endocrinology Research Center, 117036 Moscow, Russia

²Sechenov First Moscow State Medical University, 119048 Moscow, Russia

³Moscow Center for Advanced Studies, 123592 Moscow, Russia

⁴Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, Russia

⁵Lomonosov Moscow State University, 119991 Moscow, Russia

^* To whom correspondence should be addressed.

Received: December 20, 2024; Revised: July 21, 2025; Accepted: July 28, 2025

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Endocrine disorders represent a serious public health problem and frequently can be caused by genetic factors or their combination with environmental and lifestyle factors. Assessment of relevant genetic factors is important to estimate the risk of endocrine pathologies in an individual before their manifestation. Identification of genetic variations in proteins of the major histocompatibility complex is important with regard to the autoimmune nature of many endocrine pathologies, including type 1 diabetes. In this study, we investigated the relationship between human leukocyte antigen (HLA) genes and 13 endocrine disorders by using experimental whole-exome sequencing profiles obtained for 895 patients from the National Medical Research Center for Endocrinology, Moscow. In addition, the linkage disequilibrium of the identified alleles in the context of the respective diagnoses was assessed. We identified totally 45 statistically significant associations between HLA alleles and specific diagnoses of endocrine pathologies. Among them, 33 were described for the first time and 12 have been previously reported for type 1 diabetes. Overall, 17 alleles were associated with type 1 diabetes and four alleles – with other forms of diabetes. Furthermore, three alleles were associated with obesity, five – with adrenogenital diseases, three – with hypoglycemia, and three – with precocious puberty. Single alleles were found to be associated with congenital hypothyroidism without goiter, hyperfunction of pituitary gland, adrenomedullary hyperfunction, and short stature due to endocrine disorder. The study shows that early HLA typing can help in detecting genetic risk factors of endocrine disorders. In addition, identification of disease associations with specific HLA alleles can broaden our understanding of the mechanisms involved in the pathogenesis of relevant endocrine disorders.

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KEY WORDS: endocrine pathology, HLA, diabetes mellitus, obesity, congenital hypothyroidism without goiter, autoimmune disease

DOI: 10.1134/S000629792460460X

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