RHEUMATOLOGY / CLINICAL RESEARCH
Association between postmenopausal osteoporosis and the glucocorticoid receptor gene (NR3C1) BclI C/G polymorphism in a Turkish population
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1
Department of Obstetrics and Gynecology, Niğde Ömer Halisdemir University, Niğde, Turkey
2
Department of Veterinary Genetics, School of Veterinary Medicine, Ondokuz Mayis University, Samsun, Turkey
3
Department of Medical Biology, School of Medicine, Gaziosmanpaşa University, Tokat, Turkey
4
Department of Physical Therapy and Rehabilitation, Liv Hospital, Samsun, Turkey
5
Department of Physical Therapy and Rehabilitation, Private Clinic, Ankara, Turkey
Submission date: 2020-11-11
Final revision date: 2021-03-03
Acceptance date: 2021-05-02
Online publication date: 2021-05-07
Corresponding author
Bülent Çakmak
Niğde Ömer Halisdemir Üniversitesi
Department of Obstetrics and Gynecology
Niğde Ömer Halisdemir University
51100 Niğde, Turkey
Phone: +905335726978
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Glucocorticoids (GCs) are used in the treatment of numerous diseases, and long-term GC use can cause bone loss. GC receptor activation can decrease bone mineral density (BMD) by inhibiting osteoblast activity and stimulating and osteoclast activity. GC receptor gene polymorphisms have also been associated with increased susceptibility to GCs. The purpose of this study was to assess the relationship between osteoporosis and glucocorticoid receptor gene (NR3C1) polymorphism in a Turkish population.
Material and methods:
The study group consisted of 232 unrelated patients with osteoporosis and 150 unrelated healthy controls. All participants, patients and healthy controls, were of Turkish origin, from the central region of Turkey. Genomic DNA was isolated from whole venous blood samples using a commercial DNA isolation kit. The NR3C1 BclI gene C/G polymorphism was analyzed by polymerase chain reaction.
Results:
The frequencies of CC, CG, and GG genotypes in the patients were 34.5%, 48.3%, and 17.2% and in the controls were 48.0%, 42.0%, and 10.0%. A statistically significant difference in genotype frequencies was observed between patients and controls (p = 0.01). The C and G allele frequencies were 58.6% and 41.4%, respectively, in the patient group and 69.0% and 31.0%, respectively, in the control group (p = 0.005).
Conclusions:
The NR3C1 BclI gene C/G polymorphism may be associated with osteoporosis in the studied Turkish population.
REFERENCES (20)
1.
Genant HK, Cooper C, Poor G, et al. Interim report and recommendations of the World Health Organization Task-Force for Osteoporosis. Osteoporos Int 1999; 10: 259-64.
2.
Lane NE. Epidemiology, etiology, and diagnosis of osteoporosis. Am J Obstet Gynecol 2006; 194 (2 Suppl.): S3-S11.
3.
Epstein S, Inzerillo AM, Caminis J, Zaidi M. Disorders associated with acute rapid and severe bone loss. J Bone Miner Res 2003; 18: 2083-94.
4.
Wright AP, Zilliacus J, McEwan IJ, et al. Structure and function of the glucocorticoid receptor. J Steroid Biochem Mol Biol 1993; 47: 11-9.
5.
Huizenga NA, Koper JW, De Lange P, et al. A polymorphism in the glucocorticoid receptor gene may be associated with and increased sensitivity to glucocorticoids in vivo. J Clin Endocrinol Metab 1998; 83: 144-51.
6.
van Rossum EF, Koper JW, van den Beld AW, et al. Identification of the BclI polymorphism in the glucocorticoid receptor gene: Association with sensitivity to glucocorticoids in vivo and body mass index. Clin Endocrinol (Oxf) 2003; 59: 585-92.
7.
Peng YM, Lei SF, Guo Y, et al. Sex-Specific association of the glucocorticoid receptor gene with extreme BMD. J Bone Miner Res 2008; 23: 247-52.
8.
Koetz KR, van Rossum EF, Ventz M, Diederich S, Quinkler M. BclI polymorphism of the glucocorticoid receptor gene is associated with increased bone resorption in patients on glucocorticoid replacement therapy. Clin Endocrinol (Oxf) 2013; 78: 831-7.
9.
Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO study group. Osteoporos Int 1994; 4: 368-81.
10.
Morrison NA, Yeoman R, Kelly PJ, Eisman JA. Contribution of trans-acting factors alleles to normal physiological variability: Vitamin D receptor gene polymorphisms and circulating osteocalcin. Proc Natl Acad Sci 1992; 89: 6665-9.
11.
Smith EP, Boyod J, Frank GR, et al. Estrogen resistance caused by a mutation in the estrogen receptor gene in a man. New Engl J Med 1994; 331: 1056-61.
12.
Zmuda MJ, Cauley JA, Kuller LH, et al. Androgen receptor CAG repeat length is associated with increased hip bone loss and vertebral fracture risk among older men, in: Proceedings of the ASBMR 22nd Annual Meeting. J Bone Miner Res 2001; 15: 491.
13.
Canalis E. Mechanisms of glucocorticoid action on bone: implications to glucocorticoid-induced osteoporosis. J Clin Endocrinol Metab 1996; 81: 3441-7.
14.
Centrella M, McCarthy TL, Canalis E. Glucocorticoid regulation of transforming growth factor 1 activity and binding in osteoblast-enriched cultures from fetal rat bone. Mol Cell Biol 1991; 11: 4490-6.
15.
Cooper MS, Hewison M, Stewart PM. Glucocorticoid activity, inactivity and the osteoblast. J Endocrinol 1999; 163: 159-64.
16.
Oursler MJ, Riggs BL, Conover CA. Glucocorticoid-induced activation of latent transforming growth factor by normal human osteoblast-like cells. Endocrinology 1993; 133: 2187-96.
17.
Stromstedt PE, Poellinger L, Gustafsson JA, Carlstedt-Duke J. The glucocorticoid receptor binds to a sequence overlapping the TATA box of the human osteocalcin promoter: a potential mechanism for negative regulation. Mol Cell Biol 1991; 11: 3379-83.
18.
Cakmak B, Inanir A, Karakus N, Ates O, Yigit S. Association between the ACE gene I/D polymorphism and osteoporosis in a Turkish population. Z Rheumatol 2015; 74: 346-50.
19.
Feldman K, Szappanos A, Butz H, et al. The rs4844880 polymorphism in the promoter region of the HSD11B1 gene associates with bone mineral density in healthy and postmenopausal osteoporotic women. Steroids 2012; 7: 1345-51.
20.
Erdogan MO, Yıldız H, Artan S, et al. Association of estrogen receptor alpha and collagen type I alpha 1 gene polymorphisms with bone mineral density in postmenopausal women. Osteoporos Int 2011; 22: 1219-25.