Single Nucleotide Polymorphism of rs1800247 in Promoter Region of Osteocalcin Gene in Patients with Medullary Thyroid Carcinoma

Document Type : Original Article (s)

Authors

1 Department of Clinical Biochemistry, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran

2 Professor, Department of Clinical Biochemistry, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran

3 Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Associate Professor, Cellular and Molecular Endocrine Research Center, Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

Background: Medullary thyroid carcinoma is a malignant tumor originated from parafollicular cells. Osteocalcin (OC) is the most non-collagenous protein in bone and its gene is located on chromosome 1 (1q25-q31). Important polymorphism in promoter region of osteocalcin gene is located at 298nt (rs1800247), in which C base is converted to T base. In this study, to evaluate the presence of this polymorphism with existence of medullary thyroid carcinoma (MTC), the rs1800247 polymorphism in promoter region of osteocalcin was studied.Methods: In a case-control study, we evaluated the single nucleotide polymorphism (SNP) of rs1800247 in osteocalcin gene promoter in 200 volunteers, including 100 cases and 100 controls, consist of 106 men and 94 women. The mean age was 35.0 ± 11.3 and 37.0 ± 13.8 years in patients and controls, respectively. Thyroid biopsies and pathology confirmation were considered as confirmation of the medullary thyroid carcinoma diagnosis. Genomic DNA was extracted from the leukocytes using the standard Salting Out/Proteinase K method. Polymorphism detection was performed by polymerase chain reaction-sequencing (PCR-sequencing) and direct DNA sequencing methods. Obtained results were statistically analyzed using logistic regression method. The confidence level considered at 95%.Findings: In patients’ population, the genotype frequency was 7%, 48%, and 45% for CC, TT, and CT, respectively; these amounts were 8%, 55%, and 37% in controls, respectively. The frequency of C allele was 29.5% in patients 35.5% in controls; and the frequency of T allele frequency was 70.5%, and 64.5% in patients and controls, respectively. There was not any statistically significant difference between the groups in any of the cases.Conclusion: There was no association between the single nucleotide polymorphism of rs1800247 in promoter region of osteocalcin gene in patients with medullary thyroid carcinoma compared with normal individuals. According to no difference between allelic and genotypic frequencies between patients and controls, the mentioned polymorphism is not suitable candidate for genetic diagnosis of medullary thyroid carcinoma.

Keywords

References

  1. Sywak M, Pasieka JL, Ogilvie T. A review of thyroid cancer with intermediate differentiation. J Surg Oncol 2004; 86(1): 44-54.
  2. Dvorakova S, Vaclavikova E, Sykorova V, Duskova J, Vlcek P, Ryska A, et al. New multiple somatic mutations in the RET proto-oncogene associated with a sporadic medullary thyroid carcinoma. Thyroid 2006; 16(3): 311-6.
  3. Marsh DJ, Learoyd DL, Robinson BG. Medullary thyroid carcinoma: recent advances and management update. Thyroid 1995; 5(5): 407-24.
  4. Moura MM, Cavaco BM, Pinto AE, Domingues R, Santos JR, Cid MO, et al. Correlation of RET somatic mutations with clinicopathological features in sporadic medullary thyroid carcinomas. Br J Cancer 2009; 100(11): 1777-83.
  5. Price PA, Parthemore JG, Deftos LJ. New biochemical marker for bone metabolism. Measurement by radioimmunoassay of bone GLA protein in the plasma of normal subjects and patients with bone disease. J Clin Invest 1980; 66(5): 878-83.
  6. Price PA, Baukol SA. 1,25-Dihydroxyvitamin D3 increases synthesis of the vitamin K-dependent bone protein by osteosarcoma cells. J Biol Chem 1980; 255(24): 11660-3.
  7. Price PA, Nishimoto SK. Radioimmunoassay for the vitamin K-dependent protein of bone and its discovery in plasma. Proc Natl Acad Sci U S A 1980; 77(4): 2234-8.
  8. Ducy P. The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism. Diabetologia 2011; 54(6): 1291-7.
  9. Dohi Y, Iki M, Ohgushi H, Gojo S, Tabata S, Kajita E, et al. A novel polymorphism in the promoter region for the human osteocalcin gene: the possibility of a correlation with bone mineral density in postmenopausal Japanese women. J Bone Miner Res 1998; 13(10): 1633-9.
  10. Koeneman KS, Kao C, Ko SC, Yang L, Wada Y, Kallmes DF, et al. Osteocalcin-directed gene therapy for prostate-cancer bone metastasis. World J Urol 2000; 18(2): 102-10.
  11. Wu HC, Lin CC, Chen WC, Chen HY, Tsai FJ. Osteocalcin gene HindIII C/T polymorphism is a biomarker for prostate cancer and responsiveness to hormone therapy. Eur Urol 2003; 43(2): 197-200.
  12. Simionescu L, Dumitriu L, Dimitriu V, Zamfir-Grigorescu D, Campean G, Dumitriu E, et al. The serum osteocalcin levels in patients with thyroid diseases. Endocrinologie 1988; 26(1): 27-33.
  13. Lian J, Stewart C, Puchacz E, Mackowiak S, Shalhoub V, Collart D, et al. Structure of the rat osteocalcin gene and regulation of vitamin D-dependent expression. Proc Natl Acad Sci USA 1989; 86(4): 1143-7.
  14. Ainahi A, Kebbou M, Timinouni M, Benabdeljalil N, Fechtali T, Oufara S, et al. Study of the RET gene and his implication in thyroid cancer: Morocco case family. Indian J Cancer 2006; 43(3): 122-6.
  15. Jackson CE, Tashjian AH, Jr., Block MA. Detection of medullary thyroid cancer by calcitonin assay in families. Ann Intern Med 1973; 78(6): 845-52.
  16. Wohllk N, Schweizer H, Erlic Z, Schmid KW, Walz MK, Raue F, et al. Multiple endocrine neoplasia type 2. Best Pract Res Clin Endocrinol Metab 2010; 24(3): 371-87.
  17. Prazeres HJ, Rodrigues F, Figueiredo P, Naidenov P, Soares P, Bugalho MJ, et al. Occurrence of the Cys611Tyr mutation and a novel Arg886Trp substitution in the RET proto-oncogene in multiple endocrine neoplasia type 2 families and sporadic medullary thyroid carcinoma cases originating from the central region of Portugal. Clin Endocrinol (Oxf ) 2006; 64(6): 659-66.
  18. Chang CF, Yang WS, Su YN, Wu IL, Chang TC. Mutational spectrum of multiple endocrine neoplasia type 2 and sporadic medullary thyroid carcinoma in taiwan. J Formos Med Assoc 2009; 108(5): 402-8.
  19. Machens A, Hauptmann S, Dralle H. Modification of multiple endocrine neoplasia 2A phenotype by cell membrane proximity of RET mutations in exon 10. Endocr Relat Cancer 2009; 16(1): 171-7.
  20. Toivonen J, Tahtela R, Laitinen K, Risteli J, Valimaki MJ. Markers of bone turnover in patients with differentiated thyroid cancer with and following withdrawal of thyroxine suppressive therapy. Eur J Endocrinol 1998; 138(6): 667-73.
  21. Hoffmann HM, Beumer TL, Rahman S, McCabe LR, Banerjee C, Aslam F, et al. Bone tissue-specific transcription of the osteocalcin gene: role of an activator osteoblast-specific complex and suppressor hox proteins that bind the OC box. J Cell Biochem 1996; 61(2): 310-24.
  22. Lin GT, Tseng HF, Chang CK, Chuang LY, Liu CS, Yang CH, et al. SNP combinations in chromosome-wide genes are associated with bone mineral density in Taiwanese women. Chin J Physiol 2008; 51(1): 32-41.
  23. Das SK, Sharma NK, Elbein SC. Analysis of osteocalcin as a candidate gene for type 2 diabetes (T2D) and intermediate traits in Caucasians and African Americans. Dis Markers 2010; 28(5): 281-6.
Journal of Isfahan Medical School
Volume 32, Issue 276 - Serial Number 276
January and February 2014
Pages 220-227

Files

History

  • Receive Date: 26 November 2013
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics