Major thrombophilic mutations have been identified as risk factors for nontraumatic osteonecrosis of the femoral head (ONFH) in Caucasians. We asked whether the genetic background of patients with ONFH in the Korean population was similar. We analyzed factor V G1691A mutation (factor V Leiden), prothrombin G20210A mutation, and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in 71 patients (53 men, 18 women) with ONFH. We classified these patients as 51 alcohol-induced, 18 idiopathic, one steroid-induced, and one dysbaric. We recruited 200 normal control subjects (128 men, 72 women). We used multiplex PCR/restriction fragment length polymorphism for each genotyping. We observed neither factor V Leiden nor prothrombin G20210A mutation. Although methylenetetrahydrofolate reductase A1298C genotypes were not associated with osteonecrosis, methylenetetrahydrofolate reductase C677T variant genotypes increased the risk of ONFH compared with 677CC. Odds ratios of 677CT and 677CT+TT were 2.00 (95% confidence interval, 1.05–3.81) and 1.96 (95% confidence interval, 1.07–3.59), respectively, compared with 677CC. Our data suggest methylenetetrahydrofolate reductase C677T polymorphism plays a role in the pathogenesis of osteonecrosis in the Korean population. It also implies the genetic risk profile of ONFH may differ among ethnic populations.
Level of Evidence: Level II, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.
Osteonecrosis Factor Versus Korean Population Normal Control Subject MTHFR C677T
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.
We thank Tae Young Kang, MT, for his excellent technical assistance.
Angchaisuksiri P, Pingsuthiwong S, Aryuchai K, Busabaratana M, Sura T, Atichartakarn V, Sritara P. Prevalence of the G1691A mutation in the factor V gene (factor V Leiden) and the G21210A prothrombin gene mutation in the Thai population. Am J Hematol. 2000;65:119–122.PubMedCrossRefGoogle Scholar
Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature. 1994;369:64–67.PubMedCrossRefGoogle Scholar
Bjorkman A, Burtscher IM, Svensson PJ, Hillarp A, Besjakov J, Benoni G. Factor V Leiden and the prothrombin 20210A gene mutation and osteonecrosis of the knee. Arch Orthop Trauma Surg. 2005;125:51–55.PubMedCrossRefGoogle Scholar
Bjorkman A, Svensson PJ, Hillarp A, Burtscher IM, Rünow A, Benoni G. Factor V Leiden and prothrombin gene mutation: risk factors for osteonecrosis of the femoral head in adults. Clin Orthop Relat Res. 2004;425:168–172.PubMedCrossRefGoogle Scholar
Chang JD, Lee SH, Oh SY, Wi YH, Lee JS. The risk factors associated with alcohol-induced osteonecrosis of the femoral head [in Korean]. J Korean Orthop Assoc. 2004;39:692–699.Google Scholar
den Heijer M, Koster T, Blom HJ, Bos GM, Briet E, Reitsma PH, Vandenbroucke JP, Rosendaal FR. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N Engl J Med. 1996;334:759–762.CrossRefGoogle Scholar
De Stefano V, Chiusolo P, Paciaroni K, Leone G. Epidemiology of factor V Leiden: clinical implications. Semin Thromb Hemost. 1998;24:367–379.PubMedCrossRefGoogle Scholar
Gardeniers JWM. A new international classification of osteonecrosis of the ARCO Committee on terminology and classification. J Jpn Orthop Assoc. 1992;66:18–20.Google Scholar
Glueck CJ, Freiberg RA, Fontaine RN, Tracy T, Wang P. Hypofibrinolysis, thrombophilia, osteonecrosis. Clin Orthop Relat Res. 2001;386:19–33.PubMedCrossRefGoogle Scholar
Glueck CJ, Freiberg RA, Tracy T, Stroop D, Wang P. Thrombophilia and hypofibrinolysis: pathophysiologies of osteonecrosis. Clin Orthop Relat Res. 1997;334:43–56.PubMedCrossRefGoogle Scholar
Han CD, Choe WS, Yoo JH. Effect of polyethylene wear on osteolysis in cementless primary total hip arthroplasty: minimal 5-year follow-up study. J Arthroplasty. 1999;14:714–723.PubMedCrossRefGoogle Scholar
Hirota Y, Hotokebuchi T, Sugioka Y. Idiopathic osteonecrosis of the femoral head: nationwide epidemiologic studies in Japan. In: Urbiniak JR, Jones JP Jr, eds. Osteonecrosis: Etiology, Diagnosis, Treatment. Rosemont IL: American Academy of Orthopaedic Surgeons; 1997:51–58.Google Scholar
Hong SH, Song J, Kim JQ. Genetic variation of the methylenetetrahydrofolate reductase and cystathionine beta-synthase genes in Korean patients with coronary artery disease and a new polymorphism in intron 7. Mol Cell Probes. 2001;15:119–123.PubMedCrossRefGoogle Scholar
Hsu LA, Ko YL, Wang SM, Chang CJ, Hsu TS, Chiang CW, Lee YS. The C677T mutation of the methylenetetrahydrofolate reductase gene is not associated with the risk of coronary artery disease or venous thrombosis among Chinese in Taiwan. Hum Hered. 2001;51:41–45.PubMedCrossRefGoogle Scholar
Jones LC, Mont MA, Le TB, Petri M, Hungerford DS, Wang P, Glueck CJ. Procoagulants and osteonecrosis. J Rheumatol. 2003;30:783–791.PubMedGoogle Scholar
Jun ZJ, Ping T, Lei Y, Li L, Ming SY, Jing W. Prevalence of factor V Leiden and prothrombin G20210A mutations in Chinese patients with deep vein thrombosis and pulmonary embolism. Clin Lab Haematol. 2006;28:111–116.PubMedCrossRefGoogle Scholar
Kim YH, Kim VE. Uncemented porous-coated anatomic total hip replacement: results at six years in a consecutive series. J Bone Joint Surg Br. 1993;75:6–13.PubMedGoogle Scholar
Kim YW, Yoon KY, Park S, Shim YS, Cho HI, Park SS. Absence of factor V Leiden mutation in Koreans. Thromb Res. 1997;86:181–182.PubMedCrossRefGoogle Scholar
Lee JS, Koo KH, Ha YC, Koh KK, Kim SJ, Kim JR, Song HR, Cho SH. Role of thrombotic and fibrinolytic disorders in osteonecrosis of the femoral head. Clin Orthop Relat Res. 2003;417:270–276.PubMedGoogle Scholar
Lu Y, Zhao Y, Liu G, Wang X, Liu Z, Chen B, Hui R. Factor V gene G1691A mutation, prothrombin gene G20210A mutation, and MTHFR gene C677T mutation are not risk factors for pulmonary thromboembolism in Chinese population. Thromb Res. 2002;106:7–12.CrossRefGoogle Scholar
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215–1218.PubMedCrossRefGoogle Scholar
Salvati EA, Della Valle AG, Westrich GH, Rana AJ, Specht L, Weksler BB, Wang P, Glueck CJ. The John Charnley Award: heritable thrombophilia and development of thromboembolic disease after total hip arthroplasty. Clin Orthop Relat Res. 2005;441:40–55.PubMedCrossRefGoogle Scholar
Wisotzkey JD, Bell T, Monk JS. Simultaneous polymerase chain reaction restriction fragment length polymorphism identification of the factor V Leiden allele and the prothrombin 20210A mutation. Diagn Mol Pathol. 1998;7:180–183.PubMedCrossRefGoogle Scholar
Yi P, Pogribny IP, James SJ. Multiplex PCR for simultaneous detection of 677 C→T and 1298 A→C polymorphisms in methylenetetrahydrofolate reductase gene for population studies of cancer risk. Cancer Lett. 2002;181:209–213.PubMedCrossRefGoogle Scholar
Zalavras C, Dailiana Z, Elisaf M, Bairaktari E, Vlachogiannopoulos P, Katsaraki A, Malizos KN. Potential aetiological factors concerning the development of osteonecrosis of the femoral head. Eur J Clin Invest. 2000;30:215–221.PubMedCrossRefGoogle Scholar
Zalavras CG, Malizos KN, Dokou E, Vartholomatos G. The 677C→T mutation of the methylene-tetrahydrofolate reductase gene in the pathogenesis of osteonecrosis of the femoral head. Haematologica. 2002;87:111–112.PubMedGoogle Scholar
Zalavras CG, Vartholomatos G, Dokou E, Malizos KN. Factor V Leiden and prothrombin gene mutations in femoral head osteonecrosis. Thromb Haemost. 2002;87:1079–1080.PubMedGoogle Scholar
Zalavras CG, Vartholomatos G, Dokou E, Malizos KN. Genetic background of osteonecrosis. Associated with thrombophilic mutations? Clin Orthop Relat Res. 2004;422:251–255.PubMedCrossRefGoogle Scholar