Evaluation of rs3102735 and rs2073617 Osteoprotegerin Gene Polymorphisms and the Risk of Childhood Acute lymphoblastic Leukemia in Zahedan Southeast Iran
Abstract
Introduction: Osteoprotegerin (OPG), a soluble decoy receptor secreted by osteoblasts, binds RANK-L, preventing stimulation of osteoclastogenesis. In the present study we aimed to investigate the impact of OPG variants and susceptibility to childhood acute lymphocytic leukemia (ALL) in a sample of Iranian population.
Methods: This case-control study was done on 98 ALL and 124 healthy children. We genotyped the polymorphisms using tetra-primer ARMS-PCR (T-ARMS-PCR).
Results: Our findings showed that neither rs3102735 nor rs2073617 variants were associated with ALL in a sample of Iranian population. Concerning rs3102735 polymorphism, the age of ALL predispositions was significantly higher in TC+CC genotype than TT genotype (P=0.032). Furthermore, the CSF involvement was significantly higher in ALL subjects carrying TC+CC genotype (p=0.044).
Conclusion: We found no association between OPG (rs3102735, rs2073617) gene polymorphisms and risk of childhood ALL. Further studies with larger sample sizes and various ethnicities are necessary to verify our findings.
Canalle R, Burim RV, Tone LG, Takahashi CS. Genetic polymorphisms and susceptibility to childhood acute lymphoblastic leukemia. Environ Mol Mutagen. 2004;43(2):100-9.
Wittrant Y, Theoleyre S, Chipoy C, Padrines M, Blanchard F, Heymann D, et al. RANKL/RANK/OPG: new therapeutic targets in bone tumours and associated osteolysis. Biochim Biophys Acta. 2004;1704(2):49-57.
Bhatia P, Sanders MM, Hansen MF. Expression of receptor activator of nuclear factor-kappaB is inversely correlated with metastatic phenotype in breast carcinoma. Clin Cancer Res. 2005;11(1):162-5.
Heider U, Langelotz C, Jakob C, Zavrski I, Fleissner C, Eucker J, et al. Expression of receptor activator of nuclear factor kappaB ligand on bone marrow plasma cells correlates with osteolytic bone disease in patients with multiple myeloma. Clin Cancer Res. 2003;9(4):1436-40.
Kong YY, Feige U, Sarosi I, Bolon B, Tafuri A, Morony S, et al. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature. 1999;402(6759):304-9.
Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93(2):165-76.
Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, et al. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature. 1997;390(6656):175-9.
Fata JE, Kong YY, Li J, Sasaki T, Irie-Sasaki J, Moorehead RA, et al. The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development. Cell. 2000;103(1):41-50.
Hsu H, Lacey DL, Dunstan CR, Solovyev I, Colombero A, Timms E, et al. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci U S A. 1999;96(7):3540-5.
Min JK, Kim YM, Kim YM, Kim EC, Gho YS, Kang IJ, et al. Vascular endothelial growth factor up-regulates expression of receptor activator of NF-kappa B (RANK) in endothelial cells. Concomitant increase of angiogenic responses to RANK ligand. J Biol Chem. 2003;278(41):39548-57.
Santini D, Perrone G, Roato I, Godio L, Pantano F, Grasso D, et al. Expression pattern of receptor activator of NFkappaB (RANK) in a series of primary solid tumors and related bone metastases. J Cell Physiol. 2011;226(3):780-4.
Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, De Smedt T, et al. RANK is essential for osteoclast and lymph node development. Genes Dev. 1999;13(18):2412-24.
Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999;397(6717):315-23.
Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89(2):309-19.
Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A. 1998;95(7):3597-602.
Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, et al. osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev. 1998;12(9):1260-8.
McGonigle JS, Giachelli CM, Scatena M. Osteoprotegerin and RANKL differentially regulate angiogenesis and endothelial cell function. Angiogenesis. 2009;12(1):35-46.
Hofbauer LC, Schoppet M. Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA. 2004;292(4):490-5.
Corey E, Brown LG, Kiefer JA, Quinn JE, Pitts TE, Blair JM, et al. Osteoprotegerin in prostate cancer bone metastasis. Cancer Res. 2005;65(5):1710-8.
Zhang J, Dai J, Qi Y, Lin DL, Smith P, Strayhorn C, et al. Osteoprotegerin inhibits prostate cancer-induced osteoclastogenesis and prevents prostate tumor growth in the bone. J Clin Invest. 2001;107(10):1235-44.
Narita N, Yuasa T, Tsuchiya N, Kumazawa T, Narita S, Inoue T, et al. A genetic polymorphism of the osteoprotegerin gene is associated with an increased risk of advanced prostate cancer. BMC Cancer. 2008;8(224.
Ney JT, Juhasz-Boess I, Gruenhage F, Graeber S, Bohle RM, Pfreundschuh M, et al. Genetic polymorphism of the OPG gene associated with breast cancer. BMC Cancer. 2013;13(40.
Hasani SS, Hashemi M, Eskandari-Nasab E, Naderi M, Omrani M, Sheybani-Nasab M. A functional polymorphism in the miR-146a gene is associated with the risk of childhood acute lymphoblastic leukemia: a preliminary report. Tumour Biol. 2014;35(1):219-25.
Hashemi M, Moazeni-Roodi AK, Fazaeli A, Sandoughi M, Bardestani GR, Kordi-Tamandani DM, et al. Lack of association between paraoxonase-1 Q192R polymorphism and rheumatoid arthritis in southeast Iran. Genet Mol Res. 2010;9(1):333-9.
Hashemi M, Moazeni-Roodi A, Bahari A, Taheri M. A Tetra-Primer Amplification Refractory Mutation System-Polymerase Chain Reaction for the Detection of rs8099917 IL28B Genotype. Nucleosides Nucleotides Nucleic Acids. 2012;31(1):55-60.
Hashemi M, Hanafi Bojd H, Eskandari Nasab E, Bahari A, Hashemzehi NA, Shafieipour S, et al. Association of Adiponectin rs1501299 and rs266729 Gene Polymorphisms With Nonalcoholic Fatty Liver Disease. Hepat Mon. 2013;13(5):e9527.
Hashemi M, Eskandari-Nasab E, Zakeri Z, Atabaki M, Bahari G, Jahantigh M, et al. Association of pre-miRNA-146a rs2910164 and premiRNA-499 rs3746444 polymorphisms and susceptibility to rheumatoid arthritis. Mol Med Report. 2013;7(287-91.
Luo Y, Hu Z, Hao J, Jiang W, Shen J, Zhao J. Significant Associations Between the A163G and G1181C Polymorphisms of the Osteoprotegerin Gene and Risk of Osteoporosis, Especially in Postmenopausal Women: A Meta-Analysis. Genet Test Mol Biomarkers. 2014;
Guo L, Tang K, Quan Z, Zhao Z, Jiang D. Association Between Seven Common OPG Genetic Polymorphisms and Osteoporosis Risk: A Meta-Analysis. DNA Cell Biol. 2014;33(1):29-39.
Hussien YM, Shehata A, Karam RA, Alzahrani SS, Magdy H, El-Shafey AM. Polymorphism in vitamin D receptor and osteoprotegerin genes in Egyptian rheumatoid arthritis patients with and without osteoporosis. Mol Biol Rep. 2013;40(5):3675-80.
Guo C, Hu F, Zhang S, Wang Y, Liu H. Association between osteoprotegerin gene polymorphisms and cardiovascular disease in type 2 diabetic patients. Genet Mol Biol. 2013;36(2):177-82.
Choe WS, Kim HL, Han JK, Choi YE, Seo B, Cho HJ, et al. Association between OPG, RANK and RANKL gene polymorphisms and susceptibility to acute coronary syndrome in Korean population. J Genet. 2012;91(1):87-9.
Santini D, Schiavon G, Vincenzi B, Gaeta L, Pantano F, Russo A, et al. Receptor activator of NF-kB (RANK) expression in primary tumors associates with bone metastasis occurrence in breast cancer patients. PLoS One. 2011;6(4):e19234.
Sonmez M, Kazaz N, Yucel B, Topbas M, Ucar F. C950T and C1181G osteoprotegerin gene polymorphisms in myeloma bone disease. Hematology. 2013;
Bao BY, Lin VC, Huang SH, Pao JB, Chang TY, Lu TL, et al. Clinical significance of tumor necrosis factor receptor superfamily member 11b polymorphism in prostate cancer. Ann Surg Oncol. 2010;17(6):1675-81
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Issue | Vol 8, No 4 (2014) | |
Section | Articles | |
Keywords | ||
Acute lymphocytic leukemia OPG Osteoprotegerin Polymorphism |
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