Molecular Study of Bcl1 (+647 C/G) Glucocorticoid Receptor Polymorphism of Some Iraqi Patients with Type 2 Diabetes Mellitus doi.org/10.26538/tjnpr/v5i3.6

Article Sidebar

PDF DOI
Published: Mar 1, 2021
Keywords:
Bcl1 glucocorticoid receptor, Polymorphism, Type 2 Diabetes mellitus, T-ARMS PCR

Main Article Content

Wasan N. Husain
Chemistry Department, College of Education for pure Science, Tikrit University, Iraq
Adnan F. AL-Azzawie
Biology Department, College of Science, Tikrit University, Iraq
Susan J. Ali
Chemistry Department, College of Education for pure Science, Tikrit University, Iraq
Husam I. Al-muslah
Chemistry Department, College of Education, Al-Iraqia University, Iraq

Abstract

BclI is one of the polymorphisms of glucocorticoid receptor (GR) gene that is associated with increased insulin resistance. The aim of this study was to evaluate the prevalence of Bcl1 (+647C/G) polymorphism of the glucocorticoid receptor gene in Iraqi patients with type 2 diabetes mellitus (T2DM) and correlate it with levels of some biochemical parameters. In the study, 70 blood samples were collected from type 2 diabetic patients, and 50 blood samples from healthy individual as a control group. Biochemical parameters such as insulin, glutathione, ceruloplasmin and lipid profiles were estimated using enzymatic assays, while functional Bcl1 (+647 C/G) GR polymorphism was genotyped for both groups using a Tetra-amplification refractory mutation system polymerase chain reaction (T-ARMS PCR). The results revealed a significant increase in the levels of insulin, cholesterol and TG in the control compared with treatment groups, while there was no significant variance in the amounts of CP and HDL-C in both groups. Also, the differences in the genotype and allele frequency of Bcl1 GR polymorphism between both groups were not significant. This observation indicated a negative effect of the mutant G allele of Bcl1 GR polymorphism on T2DM patients. The finding suggests that GG genotype and allele of Bcl1 GR polymorphism may act as molecular markers of T2DM in Iraqi patients and have negative effects on insulin and other biochemical parameters. 

Article Details

How to Cite
Husain, W. N., AL-Azzawie, A. F., Ali, S. J., & Al-muslah, H. I. (2021). Molecular Study of Bcl1 (+647 C/G) Glucocorticoid Receptor Polymorphism of Some Iraqi Patients with Type 2 Diabetes Mellitus: doi.org/10.26538/tjnpr/v5i3.6. Tropical Journal of Natural Product Research (TJNPR), 5(3), 448-452. https://tjnpr.org/index.php/home/article/view/697
Issue
Vol. 5 No. 3 (2021): Tropical Journal of Natural Product Research
Section
Articles
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

References

Punthakee Z, Goldenberg R, Katz P. Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome. Can J Diabetes. 2018; 42:10-5.

Majer-Łobodzińska A and Adamiec-Mroczek J. Glucocorticoid receptor polymorphism in obesity and glucose homeostasis. Adv Clin Exp Med Off Organ Wroclaw Med Univ. 2017;26(1):143-148.

Di Dalmazi G, Pagotto U, Pasquali R, Vicennati V. Glucocorticoids and type 2 diabetes: From physiology to pathology. J Nutr Metab. 2012; 2012:9.

Kamba A, Daimon M, Murakami H, Otaka H, Matsuki K, Sato E, et al. Association between higher serum cortisol levels and decreased insulin secretion in a general population. PLoS One. 2016; 11(11):1-10.

Moraitis AG, Block T, Nguyen D, Belanoff JK. The role of glucocorticoid receptors in metabolic syndrome and psychiatric illness. J Steroid Biochem Mol Biol. 2017; 165:114-120.

Mamza YP and YPM. Evaluation of serum cortisol and growth hormone in type 2 diabetic subjects attending University of Maiduguri Teaching Hospital, Nigeria. IOSR J Dent Med Sci. 2013; 7(1):53-57.

Ogasawara K, Sato M, Hashimoto K, Imamura T, Go H, Hosoya M. A polymorphism in the glucocorticoid receptor gene is associated with refractory hypotension in premature infants. Pediatr Neonatol [Internet]. 2018; 59(3):251-257.

Zhao Z, Xue Y, Hong D, Zhang H, Hu Z, Fan S, Chen H.Polymorphisms in the glucocorticoid receptor gene and associations with glucocorticoid-induced avascular osteonecrosis of the femoral head. Genet Test Mol Biomarkers. 2017; 21(5):322-327.

Panek M, Pietras T, Antczak A, Górski P, Kuna P, Szemraj J. The role of functional single nucleotide polymorphisms of the human glucocorticoid receptor gene NR3C1 in Polish patients with bronchial asthma. Mole Bio Reports. 2012; 39:4749-4757.

Tissing WJE, Meijerink JPP, Den Boer ML, Brinkhof B, Van Rossum EFC, Van Wering ER, Pieters R. Genetic variations in the glucocorticoid receptor gene are not related to glucocorticoid resistance in childhood acute lymphoblastic leukemia. Clin Cancer Res. 2005; 11(16):6050-6056.

Souza MCLA, Martins CS, Silva Junior IM, Chriguer RS, Bueno AC, Antonini SR, Castro MD. NR3C1 polymorphisms in Brazilians of Caucasian, African, and Asian ancestry: glucocorticoid sensitivity and genotype association. Arq Bras Endocrinol Metabol. 2014; (58)1:53-61.

Eldeeb H, Elsawy H, El-Bendary A, Shahba A, Mostafa T. A Study of Glucocorticoid Receptor Gene Polymorphism (BclI) in Egyptian patients with Rheumatoid Arthritis. Biochem Lett. 2018; 14(1):30-39.

Namazi S, Zareifar S, Monabati A, Ansari S, Karimzadeh I. Evaluating the effect of 3 glucocorticoid receptor gene polymorphisms on risk of relapse in 100 Iranian children with acute lymphoblastic leukemia: A case-control study. Clin Ther [Internet]. 2011; 33(3):280-290.

Trementino L, Appolloni G, Concettoni C, Cardinaletti M, Boscaro M, Arnaldi G. Association of glucocorticoid receptor polymorphism A3669G with decreased risk of developing diabetes in patients with Cushing’s syndrome. Eur J Endocrinol. 2012; 166(1):35-42.

Sivapalan P, Borresen SW, Eklöf J, Klose M, Holm FS, FeldtRasmussen U, Jensen JUS. Polymorphisms of the Glucocorticoid Receptor Gene and Adrenal Suppression in Patients with Chronic Obstructive Pulmonary Disease Treated with Glucocorticoids for Acute Exacerbations. 2020.

Osman HM, Moustafa KAAE, Riad NM, Shaaban HH, El Basha NR. The effect of BclI polymorphism of NR3C1 gene on asthma phenotypes in Egyptian children. Egypt J Pediatr Allergy Immunol. 2020; 18(2):71-77.

Van Raalte DH, van Leeuwen N, Simonis-Bik AM, Nijpels G, vanHaeften TW, Schafer SA, Hart LM. Glucocorticoid receptor gene polymorphisms are associated with reduced first-phase glucosestimulated insulin secretion and disposition index in women, but not in men. Diabet Med. 2012; 29(8):211-216.

Naito HK and Kaplan A. Cholesterol, Clin. Chem. The C.V. Mosby Co. St Louis. Toronto. Princeton. 1984; 1194- 11206 and 437; 1207-1213 and 437.

Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972; 18:499-502.

Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med. 1963; 61:882-888.

Reid MA, Latour MG, Legare DJ, Rong N, Lautt WW. Comparison of the rapid insulin sensitivity test (RIST), the insulin tolerance test (ITT), and the hyperinsulinemic euglycemic clamp (HIEC) to measure insulin action in rats. Can J Physiol Pharmacol. 2002; 80(8):811-818.

Rydén, Lars. "Ceruloplasmin." Copper proteins and copper enzymes. CRC press. 2018; 37-100.

Ali SM, Mahnaz S, Mahmood T. Rapid genomic DNA extraction (RGDE). Forensic Science International: Genetics Supplement Series. 2008; 1(1):63-65.

Koetz KR, Van Rossum EFC, 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(6):831-837.

Kahn SE. The relative contributions of insulin resistance and betacell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia. 2003; 46:3-19.

Nita M, and Grzybowski A. The Role of the Reactive Oxygen Species and Oxidative Stress in the Pathomechanism of the AgeRelated Ocular Diseases and Other Pathologies of the Anterior and Posterior Eye Segments in Adults. Oxid Med Cell Longev. 2016; 2016.

Ceriello A. Oxidative stress and glycemic regulation. Metabolism. 2000; 49(2-1):27-29.

Daimon M, Susa S, Yamatani K, Manaka H, Hama K, Kimura M, Kato T. Hyperglycemia is a factor for an increase in serum ceruloplasmin in type 2 diabetes. Diabetes Care. 1998; 21(9):1525-1528.

Memişoğullari R and Bakan E. Levels of ceruloplasmin, transferrin, and lipid peroxidation in the serum of patients with Type 2 diabetes mellitus. J Diabetes Complications. 2004; 18(4):193-197.

Smith S and Lall AM. A study on lipid profile levels of diabetics and non- diabetics among Naini Region of Allahabad, India. Turk J Biochem 2008; 33(4):138-141.

Whirledge SD, Jewell CM, Barber LM, Xu X, Katen KS, Garantziotis S, Cidlowski JA. Generating diversity in human glucocorticoid signaling through a racially diverse polymorphism in the beta isoform of the glucocorticoid receptor. Lab Investig. 2017; 97(11):1282-1295.

Olczak E, Kuryłowicz A, Wicik Z, Kołodziej P, CąkałaJakimowicz M, Buyanovskaya O, et al. lucocorticoid receptor (NR3C1) gene polymorphisms are associated with age and blood parameters in Polish Caucasian nonagenarians and centenarians. Exp Gerontol. 2019; 116:20-24.

Geelen CC, van Greevenbroek MM, van Rossum EF, Schaper NC, Nijpels, G, Hart LM. Bcl I Glucocorticoid receptor polymorphism is associated with greater body fatness: The Hoorn and CODAM studies. J Clin Endocrinol Metab. 2013; 98(3):E595-E599.

Andrew R, Gale CR, Walker BR, Seckl JR, Martyn CN. Glucocorticoid metabolism and the metabolic syndrome: associations in an elderly cohort. Exp Clin Endocrinol Diabetes. 2002; 110:284-290.