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Applied Sciences OPEN ACCESS

Association of COL1A1 Rs1800012 Gene Polymorphism with The Development of Primary Empty Sella Syndrome

Dilfuza M. Artikova
Department of Internal Medicine and Endocrinology, Tashkent State Medical University, Tashkent, 100173, Uzbekistan
Barno Kh. Shagazatova
Department of Internal Medicine and Endocrinology, Tashkent State Medical University, Tashkent, 100173, Uzbekistan
DOI Crossref DOI 10.37547/tajas/Volume08Issue05-35
tajas 2026
VOL. 8 / NO. 5 MAY
FULL TEXT PP. 245-256
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VOLUME 8
ISSUE 5
YEAR 2026
PAGES 245-256
RESEARCH OVERVIEW

Abstract

This article discusses the possible role of the COL1A1 rs1800012 polymorphism in the development of primary empty sella syndrome. Special attention is given to the relationship between this genetic variant and structural changes of the sellar diaphragm, which is an important connective tissue formation involved in the pathogenesis of the syndrome. In patients with primary empty sella syndrome, the T allele and T/T genotype were observed more frequently than in the control group, especially in cases with the complete form of the disease. These findings suggest that the COL1A1 rs1800012 polymorphism may be associated with connective tissue weakness, reduced mechanical stability of the sellar diaphragm, and progression of morphological changes. The obtained data support the view that this polymorphism may be considered as one component of a multifactorial risk model for primary empty sella syndrome.

RESEARCH TOPICS

Keywords

Empty sella syndrome polymorphism sellar diaphragm

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References

  1. Ajmal R. Empty sella: it is worth mentioning in routine MR brain imaging: a review of 200 cases from a tertiary care hospital. PJR. 2019;29(2). Available from: http://www.pakjr.com/ojs/index.php/PJR/article/view/1059
  2. Auer MK, Stieg MR, Crispin A, Sievers C, Stalla GK, Kopczak A. Primary empty sella syndrome and the prevalence of hormonal dysregulation. Dtsch Arztebl Int. 2018;115(7):99-105. doi:10.3238/arztebl.2018.0099
  3. Bendella Z, Wichtmann BD, Clauberg R, Fenske W, Fries C, Jeub M, Minnerop M, et al. Structural MRI biomarkers of intracranial pressure in IIH: linking optic nerve sheath, pituitary morphology, and hormonal changes. Clin Neuroradiol. 2026. doi:10.1007/s00062-026-01618-8
  4. Braiteh N, Breiteh N, Kashou HE. Sinus bradycardia as a rare and unusual presentation of partial empty sella syndrome: a case report. Am J Case Rep. 2019;20:1071-1074. doi:10.12659/AJCR.916812
  5. Carosi G, Brunetti A, Mangone A, Baldelli R, Tresoldi A, Sindaco GD, Lavezzi E, et al. A multicenter cohort study in patients with primary empty sella: hormonal and neuroradiological features over a long follow-up. Front Endocrinol. 2022;13:925378. doi:10.3389/fendo.2022.925378
  6. Chiboub M, Mnif F, Ben Miloud B, Salah DB, Rekik N, Mohamed A. The primary empty sella: an endocrine study on 36 cases. World J Adv Res Rev. 2021;11(2):124-129. doi:10.30574/wjarr.2021.11.2.0371
  7. Chiloiro S, Giampietro A, Bianchi A, Tartaglione T, Capobianco A, Anile C, De Marinis L. Diagnosis of endocrine disease: primary empty sella: a comprehensive review. Eur J Endocrinol. 2017;177(6). doi:10.1530/EJE-17-0505
  8. Ekhzaimy A, Mujammami M, Tharkar S, Alansary MA, Al Otaibi DA. Clinical presentation, evaluation and case management of primary empty sella syndrome: a retrospective analysis of 10-year single-center patient data. BMC Endocr Disord. 2020;20(1):142. doi:10.1186/s12902-020-00621-5
  9. Ghosh D. When the sella is empty: navigating empty sella syndrome. J Assoc Clin Endocrinol Diabetol Bangladesh. 2025. doi:10.3329/jacedb.v4i20.84884
  10. Ismail Z, Amar S, Rafi S, El Mghari G, El Ansari N. A clinical case of a primary partial empty sella presenting with hypogonadotropic hypogonadism. Int J Adv Res. 2024;12(4):65-68. doi:10.21474/IJAR01/18518
  11. Kałuża B, Furmanek M, Domański J, Żuk-Łapan A, Babula E, Poprawa I, Landowska M, et al. The influence of pituitary morphology on the occurrence of hormonal disorders in patients with empty sella or partial empty sella. Biomedicines. 2025;13(4):762. doi:10.3390/biomedicines13040762
  12. Kitamura T, Ishihara Y, Kusakabe T, Tsuiki M, Nanba K, Hiroshima-Hamanaka K, Nomura T, et al. A case of osteogenesis imperfecta caused by a COL1A1 variant, coexisting with pituitary stalk interruption syndrome. Endocr J. 2023;70(8):839-846. doi:10.1507/endocrj.EJ22-0564
  13. Kleinmann RE, Kazarian EL, Raptopoulos V, Braverman LE. Primary empty sella and Rieger’s anomaly of the anterior chamber of the eye. N Engl J Med. 1981;304(2):90-93. doi:10.1056/NEJM198101083040205
  14. Latrech H, Yagoubi L, Ourdi A, Bouichrat N, Rouf S. Empty sella syndrome: long-term impact on pituitary function. J Med Life. 2025;18(8):781-784. doi:10.25122/jml-2025-0044
  15. Li Z, Han K, Yang W, Wu B, Cao R, Chen S, Zhang X, Han X, Guo L. Case report: a patient with an empty sella accompanied by rare thyrotoxicosis. Front Endocrinol. 2025;16:1516538. doi:10.3389/fendo.2025.1516538
  16. Lundholm MD, Yogi-Morren D. A comprehensive review of empty sella and empty sella syndrome. Endocr Pract. 2024;30(5):497-502. doi:10.1016/j.eprac.2024.03.004
  17. Mahajan C, Prabhakar H, Bilotta F. Endocrine dysfunction after traumatic brain injury: an ignored clinical syndrome? Neurocrit Care. 2023;39(3):714-723. doi:10.1007/s12028-022-01672-3
  18. Mao J, Bristow J. The Ehlers-Danlos syndrome: on beyond collagens. J Clin Invest. 2001;107(9):1063-1069. doi:10.1172/JCI12881
  19. Midtlien JP, Curry BP, Chang E, Kiritsis NR, Aldridge JB, Fargen KM. Characterizing a new clinical phenotype: the co-existence of cerebral venous outflow and connective tissue disorders. Front Neurol. 2024;14:1305972. doi:10.3389/fneur.2023.1305972
  20. Monte PD, Foppiani L, Cafferata C, Marugo A, Bernasconi D. Primary “empty sella” in adults: endocrine findings. Endocr J. 2006;53(6):803-809. doi:10.1507/endocrj.K06-024
  21. Ngo EMT. Primary empty sella presenting with anterior hypopituitarism: reframing a benign radiologic finding through its endocrine consequences. AACE Endocrinol Diabetes. 2025;12(4):271-275. doi:10.1016/j.aed.2025.08.013
  22. Ouma J. Primary empty sella syndrome associated with visual deterioration salvaged by chiasmapexy: report of a case and discussion of the literature. Surg Neurol Int. 2020;11:48. doi:10.25259/SNI_309_2019
  23. Özdemir A, Erdoğan AM, Sevimoğlu Ö, Durgun EB, Ermis SA, Yalçın RS, Karaca Y, et al. Analysis of biochemical, hormonal and radiological morphological measurement values in patients with empty sella: a clinical study. Arq Bras Neurocir. 2024;43(4). doi:10.1055/s-0044-1796656
  24. Pelineagră OE, Golu I, Chiriţă-Emandi A, Balaş M, Andreescu N, Munteanu CV, Amzăr DG, et al. Intersecting pathologies: COL1A1-related syndrome in the setting of childhood-onset hypopituitarism: case report and literature review. Diagnostics. 2025;15(19):2453. doi:10.3390/diagnostics15192453
  25. Rice-Canetto TE, Carroll P, Reier L, Siddiqi J. Asymptomatic empty sella: a literature review and suggestions for evaluation in clinical practice. Cureus. 2024;16(12). doi:10.7759/cureus.75965
  26. Romero C, Nesi-França S, Radovick S. The molecular basis of hypopituitarism. Trends Endocrinol Metab. 2009;20(10):506-516. doi:10.1016/j.tem.2009.06.005
  27. Sharavii VB, Shnayder NA, Petrova MM. Candidate genes of empty sella. Personalized Psychiatry and Neurology. 2021;1(1):46-53. doi:10.52667/2712-9179-2021-1-1-46-53
  28. Singh P, Saleem H, Fernandez C, Yahia SE. P-093 Neuro-ophthalmologic and endocrine follow-up in patients with partial empty sella syndrome: a case series. PubMed Central. 2026;4. doi:10.1210/jcemcr/luaf297.073
  29. Vaccarezza M, Taurone S, Palmieri M, Galassi FM, Cofone L, Artico M, Papa V. Evolutionary and anthropological perspectives on the sella turcica: from vertebrate origins to neurosurgical relevance. J Endocrinol Invest. 2025;49(1):25-28. doi:10.1007/s40618-025-02698-y
  30. Vaičekauskytė Ž, Žiaukaitė IM, Pšemeneckienė G. Diagnostic pitfalls of empty sella syndrome: a case report. Lithuanian University of Health Sciences. 2020. Available from: https://hdl.handle.net/20.500.12512/106388
  31. Wang D, Zhang M, Guan H, Wang X. Osteogenesis imperfecta due to combined heterozygous mutations in both COL1A1 and COL1A2, coexisting with pituitary stalk interruption syndrome. Front Endocrinol. 2019;10:193. doi:10.3389/fendo.2019.00193
  32. Wang S, Qin Q, Jiang D, Xiao Y, Ye L, Jiang XX, Guo Q. Re-analysis of gene mutations found in pituitary stalk interruption syndrome and a new hypothesis on the etiology. Front Endocrinol. 2024;15:1338781. doi:10.3389/fendo.2024.1338781
  33. Westerman M, Kafkas A, Parry-Jones A, Strong S, Retzler C, Hallam G. Neurobiological and neuropsychological disturbance in EDS. Front Neurol. 2025;16:1648702. doi:10.3389/fneur.2025.1648702
  34. Winograd E, Kortz MW, Lillehei KO. Radiographic pituitary stalk disruption: a rare sequela of secondary empty sella syndrome. Surg Neurol Int. 2021;12:385. doi:10.25259/SNI_530_2021
  35. Won YD, Na MK, Kim CH, Kim JM, Cheong JH, Ryu JI, Han M. The frontal skull Hounsfield unit value can predict ventricular enlargement in patients with subarachnoid haemorrhage. Sci Rep. 2018;8(1):10178. doi:10.1038/s41598-018-28471-1