Association analysis between polymorphisms of the Coagulation factor V gene and the risk of osteonecrosis of femoral head in Korean population

INTRODUCTION Osteonecrosis (ON) of the femoral head (ONFH), a debilitating bone disease characterized by cellular death in the bone tissue, can lead to collapse of the architectural bony structure and joint function loss. Although many conditions, such as steroids, alcoholism, coagulation defects, storage diseases, marrow-infiltrating diseases, and some autoimmune diseases, can increase the risk of ONFH, the pathogenesis has not been completely elucidated. Many theories regarding pathogenesis, including intravascular coagulation, apoptosis of the osteoblasts and osteocytes, and fatty necrosis of the osteocytes, have been suggested. Among them, a vascular hypothesis is considered to be the most persuasive, which implicates a decrease in the local femoral head blood flow in ONFH pathogenesis. In support of this hypothesis, genetic mutations related to coagulation abnormalities, such as factor V Leiden mutation (G1691A, Arg506Gln) and 5, 10-methylene-tetrahydrofolate reductase (MTHFR) gene polymorphism (C677T, Ala222Val), have been examined to assess the role of genetics in ONFH risk. Three out of four studies investigating the role of the factor V Leiden mutation showed a positive correlation with ONFH in Caucasians. However, Lee et al. reported that there is no relationship between ONFH and increased thrombosis or impaired fibrinolysis in Korean patients with ONFH. Moreover, other studies have reported the absence of factor V (F5) Leiden and 20210A mutations in Koreans. It may be that there are geographic and ethnic differences in the prevalence of these mutations. Although F5 Leiden mutation is not found in the Korean population, the F5 gene is thought to play an important role in ONFH. Therefore, we performed extensive screening of the F5 gene by direct sequencing to identify the polymorphisms and mutations, and examined genetic association with ONFH risk in a Korean population.