Genetic Background of Nontraumatic Osteonecrosis of the Femoral Head in the Korean Population

Abstract

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.

Meta-analysis of Factor V Leiden G1691A polymorphism and osteonecrosis of femoral head susceptibility

“…Two studies in which the study subjects included an Asian population and conformed to the included criteria were deleted as they observed no FVL mutation in cases or controls. Chang et al (22) suggested that the FVL mutation is not a genetic risk factor for ONFH in Asians, or at least in the Korean population, which was in agreement with findings by Sun et al (24). The results obtained by these authors were consistent with previous reports, which demonstrated the absence of FVL mutation in the Chinese and Korean populations (25,26).…”

“…We were relatively conservative in selecting studies, which likely underestimated the alrealy identified association. Several articles investigating FVL met our criteria, but they were excluded as they could not provide sufficient information for calculating the ORs of the FVL mutation and be extracted (22)(23)(24). Consequently, the studies that were included in this meta-analysis strengthened the association between FVL mutation and ONFH.…”

Endothelial nitric oxide synthase gene polymorphisms and the risk of osteonecrosis of the femoral head in systemic lupus erythematosus

“…ONFH is one of the most common diseases of the hip in Korea, with higher incidence than that in other countries; it is responsible for more than half of the cases of total hip arthroplasty, whereas it is relatively rare in the Unites States [8]. In recent years, the clinical significance of ONFH in hip diseases has received much attention, but the details of its pathogenesis and epidemiology are not well understood; although it is generally assumed that venous thrombosis with blood flow obstruction to the femoral head, mediated by thrombophilia and/or hypofibrinolysis, is important in the development of ONFH [17,18].…”

“…In recent years, the clinical significance of ONFH in hip diseases has received much attention, but the details of its pathogenesis and epidemiology are not well understood; although it is generally assumed that venous thrombosis with blood flow obstruction to the femoral head, mediated by thrombophilia and/or hypofibrinolysis, is important in the development of ONFH [17,18]. At the genetic level, some genes have previously been reported as risk factors for ONFH, including a G1691A mutation in factor V (factor V Leiden), a G20210A mutation in prothrombin, and polymorphisms in 5, 10-methylenetetrahydrofolate reductase (MTHFR; C677T and A1298C) [8,19,20]. The presence of these genetic variations is associated with a hypercoagulable state, and increases the risk of thromboembolic events.…”

“…However, the association between genetic predisposition and thrombotic tendency may differ between ethnic groups. Moreover, neither the factor V Leiden (G1691A mutation in factor V), nor the prothrombin G20210A mutations have been found in the Korean population [7,8].…”