The Effect of BclI and N363S Glucocorticoid Receptor Gene (NR3C1) Polymorphisms in Turkish Patients with Type 2 Diabetes Mellitus

Year 2025, Volume: 14 Issue: 3, 282 - 292, 31.12.2025

Büşra Görgün , Leyla Açık , Naciye Selcen Bayramcı , Çağdaş Kalkan , İlhan Yetkin

https://doi.org/10.54187/jnrs.1741259

Abstract

This study aims to examine the relationship between the prevalence of glucocorticoid receptor (GR) gene polymorphisms and type 2 diabetes mellitus (T2DM) in Turkish individuals. Clinical and laboratory findings of patients diagnosed with T2DM and healthy controls were recorded, and blood samples were collected for genetic analysis. Following DNA isolation, genotyping was performed for the BclI and N363S polymorphisms of the Nuclear Subfamily 3 Group C Member 1 (NR3C1) gene using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. The genotype frequencies of the BclI (rs41423247) polymorphism showed a significant association with T2DM; the CC (34.1%) and CG (56.5%) genotypes were more frequent in the patient group compared to the control group, with a calculated risk ratio for the C allele of 4.762. No significant association was observed between the N363S (rs6195) polymorphism and T2DM (p>0.05). Overall, findings indicate that BclI polymorphism contributes to T2DM susceptibility in this population, whereas the N363S variant does not appear to influence disease risk.

Keywords

Glucocorticoid receptor gene , polymorphism , type 2 diabetes

Ethical Statement

The research was reviewed and approved by the Clinical Research Ethics Committee of Gazi University, Approval number: 190. This paper is derived from the first author’s master’s thesis supervised by the second author.

Supporting Institution

This work was supported by the Scientific Research Projects Coordination Unit at Gazi University, Grant number: 05/2013-12.

Project Number

05/2013-12

Thanks

This work was supported by the Scientific Research Projects Coordination Unit at Gazi University, Grant number: 05/2013-12.

References

• A. Kamba, M. Daimon, H. Murakami, H. Otaka, K. Matsuki, E. Sato, J. Tanabe, S.Takayasu, Y. Matsuhashi, M. Yanagimachi, K. Terui, K. Kageyama, I. Tokuda, I. Takahashi, S. Nakaji, Association between Higher Serum Cortisol Levels and Decreased Insulin Secretion in a General Population, PLoS One 11 (11) (2016) e0166077.
• N. B. Kasim, H. Z. Huri, S. R. Vethakkan, L. Ibrahim, B. M. Abdullah, Genetic polymorphisms associated with overweight and obesity in uncontrolled Type 2 diabetes mellitus, Biomarkers in Medicine 10 (4) (2016) 403–415.
• S. K. Kota, L. K. Meher, S. Jammula, S. K. Kota, K. D. Modi, Genetics of type 2 diabetes mellitus and other specific types of diabetes; its role in treatment modalities. Diabetes and Metabolic Syndrome 6 (1) (2012) 54–58.
• D. J. Magliano, E. J. Boyko, Diabetes Atlas (2025), https://diabetesatlas.org/resources/idf-diabetes-atlas-2025/, Accessed 10 June 2025.
• X. Han, Y. Wei, H. Hu, J. Wang, Z. Li, F. Wang, T. Long, J. Yuan, P. Yao, S. Wei, Y. Wang, X. Zhang, H. Guo, H. Yang, T. Wu, M. He, Genetic risk, a healthy lifestyle, and type 2 diabetes: the Dongfeng-Tongji cohort study, The Journal of Clinical Endocrinology and Metabolism 105 (4) (2020) 1242-1250.
• K. Matsuda, PCR-Based Detection Methods for Single-Nucleotide Polymorphism or Mutation: Real-Time PCR and Its Substantial Contribution Toward Technological Refinement, Advances in Clinical Chemistry 80 (2017) 45–72.
• M. A. Orlovsky, Allelic polymorphism of glucocorticoid receptor NR3C1 (GR): from molecular biology to clinical implications, Biopolymers and Cell 28 (5) (2012) 338–351.
• J. Etemadi, S. Abediazar, T. Majidi, S. Z. Vahed, R. Motavalli, B. Niknafs, M. J. Nakhjavani, Analysis of glucocorticoid receptor gene polymorphisms in kidney recipients with post-transplant diabetes, Journal of Renal Injury Prevention (2022).
• L. Feldkamp, L. Müller, T. Deutschbein, M. Detomas, S. Hahner, C. J. Strasburger, H. Künzel, A. Oßwald, L. Braun, G. Rubinstein, M. Reincke, M. Quinkler, T. Kienitz, Glucocorticoid receptor polymorphism BclI with increased glucocorticoid sensitivity has a positive influence on Quality of Life in Endogenous Cushing's syndrome in remission, European Journal of Endocrinology 188 (4) (2023) 366–374.
• K. M. Salah, M. M. Al Shafie, O. A. Gaber, M. T. Awad, Association between Glucocorticosteroid Receptor (NR3C1) Gene Polymorphism and Bronchial Asthma in Children, Zagazig University Medical Journal 26 (1) (2020) 123–132.
• Z. Kaya, S. Caglayan, M. Akkiprik, C. Aral, G. Ozisik, M. Ozata, A. Ozer, Impact of glucocorticoid receptor gene (NR3C1) polymorphisms in Turkish patients with metabolic syndrome, Journal of Endocrinological Investigation 39 (5) (2016) 557–566.
• G. Di Dalmazi, U. Pagotto, R. Pasquali, V. Vicennati, Glucocorticoids and Type 2 Diabetes: From Physiology to Pathology, Journal of Nutrition and Metabolism 2012 (1) (2012) 525093.
• E. Olczak, A. Kuryłowicz, Z. Wicik, P. Kołodziej, M. Cąkała-Jakimowicz, O. Buyanovskaya, P. Ślusarczyk, M. Mossakowska, M. Puzianowska-Kuźnicka, Glucocorticoid receptor (NR3C1) gene polymorphisms are associated with age and blood parameters in Polish Caucasian nonagenarians and centenarians, Experimental Gerontology 116 (2019) 20–24.
• V. Favero, A. Cremaschi, C. Parazzoli, A. Falchetti, A. Gaudio, L. Gennari, A. Scillitani, F. Vescini, V. Morelli, C. Aresta, I. Chiodini, Pathophysiology of Mild Hypercortisolism: From the Bench to the Bedside, International Journal of Molecular Sciences 23 (2) (2022) 673.
• L. Pizzorno, J. Pizzorno, Subclinical Hypercortisolism: An Important, Unrecognized Dysfunction, Integrative Medicine 21 (3) (2022) 8–15.
• X.-Q. Wang, Z.-X. Duan, X.-G. He, X.-Y. Zhou, Clinical relevance of the glucocorticoid receptor gene polymorphisms in glucocorticoid-induced ocular hypertension and primary open-angle glaucoma, International Journal of Ophthalmology 8 (1) (2015) 169–173.
• R. Hayashi, H. Wada, K. Ito, I. M. Adcock, Effects of glucocorticoids on gene transcription, European Journal of Pharmacology 500 (1-3) (2004) 51–62.
• R. Rosmond, G. Holm, A 5-year follow-up study of 3 polymorphisms in the human glucocorticoid receptor gene in relation to obesity, hypertension, and diabetes, Journal of the CardioMetabolic Syndrome 3 (3) (2008) 132–135.
• E. F. C. Van Rossum, J. W. Koper, A. W.van den Beld, A. G. Uitterlinden, P. Arp, W. Ester, J. A. M. J. L. Janssen, A. O. Brinkmann, F. H. De Jong, D. E. Grobbee, H. A. P. Pols, S. W. J. Lamberts, Identification of the BclI polymorphism in the glucocorticoid receptor gene: association with sensitivity to glucocorticoids in vivo, and body mass index, Clinical Endocrinology 59 (5) (2003) 585–592.
• C. C. Geelen, M. M. van Greevenbroek, E. F. van Rossum, N. C. Schaper, G. Nijpels, L. M. 't Hart, C. G. Schalkwijk, I. Ferreira, C. J. van der Kallen, H. P. Sauerwein, J. M. Dekker, C. D. Stehouwer, B. Havekes, BclI glucocorticoid receptor polymorphism is associated with greater body fatness: the Hoorn and CODAM studies, The Journal of Clinical Endocrinology and Metabolism 98 (3) (2013) E595–E599.
• N. S. Bayramci, L. Acik, Ç. Kalkan, I. Yetkin, Investigation of glucocorticoid receptor and calpain-10 gene polymorphisms in Turkish patients with type 2 diabetes mellitus, Turkish Journal of Medical Sciences 47 (5) (2017) 1568–1575.
• R. C. Y. Lin, X. L. Wang, B. Dalziel, I. D. Caterson, B. J. Morris, Association of obesity, but no diabetes or hypertension, with glucocorticoid receptor N363S variant, Obesity Research 11 (6) (2003) 802–808.
• R. Roussel, A. F. Reis, D. Dubois-Laforgue, C. Bellanné-Chantelot, J. Timsit, G. Velho, The N363S polymorphism in the glucocorticoid receptor gene is associated with overweight in subjects with type 2 diabetes mellitus, Clinical Endocrinology 59 (2) (2003) 237–241.