Browse > Article
http://dx.doi.org/10.5352/JLS.2008.18.4.427

Polymorphisms of 3-hydroxy-3-methylglutaryl Coenzyme A Reductase Gene Are Not Associated with the Osteonecrosis of Femoral Head in Korean  

Kim, Tae-Ho (Skeletal Diseases Genome Research Center, Kyungpook National University, Department of Medicine, Kyungpook University School of Medicine)
Hong, Jung-Min (Skeletal Diseases Genome Research Center, Kyungpook National University)
Lee, Sang-Han (Department of Food Science & Biotechnology, Kyungpook National University)
Park, Eui-Kyun (Skeletal Diseases Genome Research Center, Kyungpook National University, Department of Pathology and Regenerative Medicine, School of Dentistry, Kyungpook National University)
Kim, Shin-Yoon (Skeletal Diseases Genome Research Center, Kyungpook National University, Department of Orthopedic Surgery, Kyungpook National University School of Medicine)
Publication Information
Journal of Life Science / v.18, no.4, 2008 , pp. 427-434 More about this Journal
Abstract
Osteonecrosis of the femoral head (ONFH) is a multifactorial disease and certain individuals are more at risk or may be predisposed to it. An altered lipid metabolism is one of the major risk factors for osteonecrosis, especially corticosteroid therapy and alcoholism. 3-hydroxy-3-methylglutaryl coenzyme A. (HMG-CoA) reductase inhibitors, stalin used as lipid-clearing agent, have been known to decrease the risk of osteonecrosis in patients receiving steroids and affect coagulation and fibrinolysis. Therefore we evaluated the association of HMG-CoA reductase gene polymorphisms and haplotypes between osteonecrosis patients and normal controls. We directly sequenced the HMG-CoA reductase gene in 24 Korean individuals, and identified five sequence variants. Four SNPs (-6933C>T, -6045T>G, +12673G>A, and +18128C>T) were selected and genotyped in 349 male ONFH patients and 300 male control subjects. The genotypes, allele frequencies, and haplotypes of the polymorphisms in the total patients as well as in the subgroup by etiology were not significantly different from those in the control group. In addition, no significant differences between each genotype of the polymorphisms and plasma lipid level could be found in the control group. These results suggest that the polymorphisms and haplotypes of HMG-CoA reductase gene are unlikely to be associated with a susceptibility to ONFH.
Keywords
3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR); osteonecrosis; coagulation; polymorphism;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Wiesbauer, F., C. Kaun, G. Zorn, G. Maurer, K. Huber and J. Wojta. 2002. HMG CoA reductase inhibitors affect the fibrinolytic system of human vascular cells in vitro: a comparative study using different statins. Br. J. Pharmacol. 135, 284-292   DOI   ScienceOn
2 Wozney, J. M. 2002. Overview of bone morphogenetic proteins. Spine 27, S2-S8   DOI   ScienceOn
3 van Beek, E., C. Lowik, M. Karperien and S. Papapoulos. 2006. Independent pathways in the modulation of osteoclastic resorption by intermediates of the mevalonate biosynthetic pathway: The role of the retinoic acid receptor. Bone 38, 167   DOI   ScienceOn
4 Zalavras, C. G., G. Vartholomatos, E. Dokou and K. N. Malizos. 2002. Factor V Leiden and prothrombin gene mutations in femoral head osteonecrosis. Thromb. Haemost. 87, 1079-1080   DOI
5 Zalavras, C. G., G. Vartholomatos, E. Dokou and K. N. Malizos. 2004. Genetic background of osteonecrosis: associated with thrombophilic mutations? Clin. Orthop. Relat. Res. 251-255
6 Pritchett, J. W. 2001. Statin therapy decreases the risk of osteonecrosis in patients receiving steroids. Clin. Orthop. Relat. Res. 386, 173-178   DOI
7 Qin, Z. S., T. Niu and J. S. Liu. 2002. Partition-ligation-expectation- maximization algorithm for haplotype inference with single-nucleotide polymorphisms. Am. J. Hum. Genet. 71, 1242-1247   DOI   ScienceOn
8 Mundy, G., R. Garrett, S. Harris, J. Chan, D. Chen, G. Rossini, B. Boyce, M. Zhao and G. Gutierrez. 1999. Stimulation of bone formation in vitro and in rodents by statins. Science 286, 1946-1949   DOI   ScienceOn
9 Noa, M., S. Mendoza, R. Mas, N. Mendoza and F. Leon. 2004. Effect of D-003, a mixture of very high molecular weight aliphatic acids, on prednisolone-induced osteoporosis in Sprague-Dawley rats. Drugs R. D. 5, 281-290   DOI   ScienceOn
10 Miyanishi, K., T. Yamamoto, T. Irisa, A. Yamashita, S. Jingushi, Y. Noguchi and Y. Iwamoto. 2002. Bone marrow fat cell enlargement and a rise in intraosseous pressure in steroid-treated rabbits with osteonecrosis. Bone 30, 185-190   DOI   ScienceOn
11 Mont, M. A. and D. S. Hungerford. 1995. Non-traumatic avascular necrosis of the femoral head. J. Bone Joint Surg. Am. 77, 459-474   DOI
12 Lee, J. S., K. H. Koo, Y. C. Ha, K. K. Koh, S. J. Kim, J. R. Kim, H. R. Song and S. H. Cho. 2003. Role of thrombotic and fibrinolytic disorders in osteonecrosis of the femoral head. Clin. Orthop. Relat. Res. 417, 270-276
13 Livak, K. J. 1999. Allelic discrimination using fluorogenic probes and the 5' nuclease assay. Genet. Anal. 14, 143-149   DOI   ScienceOn
14 Krysiak, R., B. Okopien and Z. Herman. 2003. Effects of HMG-CoA reductase inhibitors on coagulation and fibrinolysis processes. Drugs 63, 1821-1854   DOI   ScienceOn
15 Atsumi, T. and Y. Kuroki. 1992. Role of impairment of blood supply of the femoral head in the pathogenesis of idiopathic osteonecrosis. Clin. Orthop. Relat. Res. 277, 22-30
16 Wang, G. J., J. G. Rawles, S. L. Hubbard and W. G. Stamp. 1983. Steroid-induced femoral head pressure changes and their response to lipid-clearing agents. Clin. Orthop. Relat. Res. 174, 298-302
17 Gardeniers, J. W. M. 1993. The ARCO perspective for reaching one uniform staging system of osteonecrosis, pp. 375-380, In Scoutens, A, J. Arlet, J. W. M. Gardeniers, S. P. F. Hughes (eds.), Bone Circulation and Vascularization in Normal and Pathologic Conditions. Plenum Press, New York
18 Glueck, C. J., R. Freiberg, H. I. Glueck, T. Tracy, D. Stroop and Y. Wang. 1995. Idiopathic osteonecrosis, hypofibrinolysis, high plasminogen activator inhibitor, high lipoprotein (a), and therapy with Stanozolol. Am. J. Hematol. 48, 213-220   DOI   ScienceOn
19 Ferrari, P., V. Schroeder, S. Anderson, L. Kocovic, B. Vogt, D. Schiesser, H. P. Marti, R. Ganz, F. J. Frey and H. P. Kohler. 2002. Association of plasminogen activator inhibitor- 1 genotype with avascular osteonecrosis in steroid- treated renal allograft recipients. Transplantation 74, 1147-1152   DOI   ScienceOn
20 Kim, S. Y., J. S. Suh, E. K. Park, W. B. Jung, J. W. Kim, K. H. Koo and C. Y. Kim. 2003. Factor V Leiden gene mutation in femoral head osteonecrosis. J. Kor. Ortho. Res. Soc. 6, 259-264
21 Koo, K. H., R. Kim, Y. S. Kim, I. O. Ahn, S. H. Cho, H. R. Song, Y. S. Park, H. Kim and G. J. Wang. 2002. Risk period for developing osteonecrosis of the femoral head in patients on steroid treatment. Clin. Rheumatol. 21, 299-303   DOI   ScienceOn
22 Jones, J. P. Jr. 1992. Intravascular coagulation and osteonecrosis. Clin. Orthop. Relat. Res. 277, 41-53
23 Assouline-Dayan, Y., C. Chang, A. Greenspan, Y. Shoenfeld and M. E. Gershwin. 2002. Pathogenesis and natural history of osteonecrosis. Semin. Arthritis. Rheum. 32, 94-124   DOI   ScienceOn
24 Koo, K. H., J. S. Lee, Y. J. Lee, K. J. Kim, J. J. Yoo and H. J. Kim. 2006. Endothelial nitric oxide synthase gene polymorphisms in patients with nontraumatic femoral head osteonecrosis. J. Orthop. Res. 24, 1722-1728   DOI   ScienceOn
25 Undas, A., K. E. Brummel-Ziedins and K. G. Mann. 2005. Statins and blood coagulation. Arterioscler. Thromb. Vasc. Biol. 25, 287-294
26 Asano, T., K. A. Takahashi, M. Fujioka, S. Inoue, K. Ueshima, T. Hirata, M. Okamoto, Y. Satomi, H. Nishino, T. Tanaka, Y. Hirota and T. Kubo. 2004. Relationship between postrenal transplant osteonecrosis of the femoral head and gene polymorphisms related to the coagulation and fibrinolytic systems in Japanese subjects. Transplantation 77, 220-225   DOI   ScienceOn
27 Hong, J. M., T. H. Kim, S. C. Chae, K. H. Koo, Y. J. Lee, E. K. Park, J. Y. Choi, H. M. Ryoo and S. Y. Kim. 2007. Association study of hypoxia inducible factor 1alpha (HIF1alpha) with osteonecrosis of femoral head in a Korean population. Osteoarthritis Cartilage 15, 688-694   DOI   ScienceOn
28 Goldstein, J. L. and M. S. Brown. 1990. Regulation of the mevalonate pathway. Nature 343, 425-430   DOI   ScienceOn
29 Hedrick, P. W. 1987. Gametic disequilibrium measures: proceed with caution. Genetics 117, 331-341
30 Glueck, C. J., P. Wang, R. N. Fontaine, L. Sieve-Smith, T. Tracy and S. K. Moore. 1999. Plasminogen activator inhibitor activity: an independent risk factor for the high miscarriage rate during pregnancy in women with polycystic ovary syndrome. Metabolism 48, 1589-1595   DOI   ScienceOn
31 Glueck, C. J., R. A. Freiberg, R. N. Fontaine, T. Tracy and P. Wang. 2001. Hypofibrinolysis, thrombophilia, osteonecrosis. Clin. Orthop. Relat. Res. 386, 19-33   DOI   ScienceOn
32 Glueck, C. J., R. Freiberg, T. Tracy, D. Stroop and P. Wang. 1997. Thrombophilia and hypofibrinolysis: pathophysiologies of osteonecrosis. Clin. Orthop. Relat. Res. 334, 43-56
33 Moskal, J. T., R. E. Topping and L. L. Franklin. 1997. Hypercholesterolemia: an association with osteonecrosis of the femoral head. Am. J. Orthop. 26, 609-612
34 Wang, G. J., D. E. Sweet, S. I. Reger and R. C. Thompson. 1977. Fat-cell changes as a mechanism of avascular necrosis of the femoral head in cortisone-treated rabbits. J. Bone Joint Surg. Am. 59, 729-735   DOI
35 Zizic, T. M., C. Marcoux, D. S. Hungerford, J. V. Dansereau and M. B. Stevens. 1985. Corticosteroid therapy associated with ischemic necrosis of bone in systemic lupus erythematosus. Am. J. Med. 79, 596-604   DOI   ScienceOn