Genetic variation in the coagulation factor V gene and risk of femoral head osteonecrosis

Abstract

Osteonecrosis of the femoral head (ONFH) is characterized by the death of the cellular portion of the femoral head due a reduction or disruption in the blood supply. Certain studies have implicated coagulation disorders, including thrombophilia and hypofibrinolysis, in the pathogenesis of ONFH. The factor V (F5) Leiden mutation has been suggested to be a genetic risk factor for venous thromboembolism and osteonecrosis in Caucasian individuals, however, this association remains controversial in other populations. The present study aimed to identify polymorphisms of the F5 gene and performed a case‑control study in a Korean population. The F5 gene was sequenced in 24 unrelated Korean individuals, and 16 polymorphisms were detected. A total of six polymorphisms were genotyped in 423 patients with ONFH and 348 control individuals. Analysis of the association between genotyped single nucleotide polymorphisms and haplotypes and with ONFH was performed. Comparison of the ONFH samples and the control individuals using logistic regression models revealed no statistically significant difference in the frequencies of the F5 polymorphisms and haplotypes. These findings suggested that F5 polymorphisms were not significant in the susceptibility to ONFH in the Korean population.

Combined Treatment with an Anticoagulant and a Vasodilator Prevents Steroid-Associated Osteonecrosis of Rabbit Femoral Heads by Improving Hypercoagulability

“…Hematologic evidence of intraosseous hypercoagulability has been found on the basis of both human and animal studies of ON [ 24 , 25 ]. Hypercoagulability, a pathological process mediated by a variety of factors and hematological changes, plays an important role in the process of thrombus formation [ 26 ]. Moreover, steroid treatment enhances hypercoagulability, induces venous thrombosis, decreases blood circulation, and leads to ONFH [ 27 , 28 ].…”

Association of Complement Receptor 2 Gene Polymorphisms with Susceptibility to Osteonecrosis of the Femoral Head in Systemic Lupus Erythematosus

“…Although ONFH is a common complication deteriorating the treatment of SLE, details of the pathogenesis are not well established. Because venous thrombosis and resultant blood flow obstruction mediated by thrombophilia or hypofibrinolysis are generally assumed to develop ONFH [ 18 , 19 ], most of gene studies have focused on gene polymorphisms affecting the coagulation and fibrinolytic systems [ 8 , 9 ]. Recent studies, however, reported that immunologic factors might develop ONFH [ 6 , 7 ] and few genetic studies were performed to reveal their roles in the development of SLE_ONFH [ 10 ].…”

“…All reactions were performed following the manufacturer's protocol. Details regarding the PCR reaction and TaqMan assay have been described previously [ 9 ]. The fluorescence data files from each plate were collected and analyzed using automated allele-calling software (SDS 2.2, Applied Biosystems).…”

“…This implicates possible role of the disease progression itself or underlying genetics. Although some studies reported that immunologic factors including interleukins and tumor necrosis factors might develop ONFH [ 6 , 7 ], most genetic studies have focused on gene polymorphisms affecting the coagulation and fibrinolytic systems [ 8 , 9 ]. Moreover, few genetic studies were performed to reveal their roles in the development of SLE_ONFH [ 10 ].…”

Genome-wide Association Study of Idiopathic Osteonecrosis of the Femoral Head

“…In order to identify the genetic factor of IONFH, many candidate gene analyses have been performed 14 ; however, these studies have only examined specific SNPs in candidate genes related to plausible pathogenesis of ONFH, such as coagulation 15 , fibrinolysis 16 , angiogenesis 17 , hypoxic response 18 , and steroid 19 and alcohol metabolisms 20 . No definite susceptibility genes have been identified yet.…”