Prevalence of genetic risk factors related with thrombophilia and hypofibrinolysis in patients with osteonecrosis of the femoral head in Poland.

Background: The etiology of osteonecrosis of femoral head (ONFH) has not been fully elucidated. Increased intravascular coagulation and/or hypofibrinolysis have been proposed as pathogenic mechanisms. Previous reports demonstrated significant association between incidence of ONFH and polymorphisms of genes related with thrombophilia especially in Caucasian subjects. The aim of our study was to evaluate the relationship between genetic mutations leading to coagulation disorders and ONFH in Polish patients.

Methods: We have investigated the frequencies of four markers among 68 unrelated individuals with clinically and radiographically documented ONFH and among 100 healthy unrelated blood donors in Eastern part of Poland. The three genes were involved in thrombophilia: factor V Leiden (G1691A), prothrombin (G20210A), Methylenetetrahydrofolate Reductase (MTHFR C677T) and one in hypofibrinolysis: Tissue Plasminogen Activator (PLAT TPA25 I/D). The samples were genotyped with polymerase chain reaction followed by restriction enzyme analysis for the restriction fragment length polymorphisms. The allele and genotype frequencies were analyzed in the relation to ONFH etiology (idiopathic and secondary), gender, age (patients younger or older than 50 years) and the number of affected joints (unilateral or bilateral ONFH).

Results: No significant difference in allele frequencies between patients and control groups were observed in genes involved in thrombophilia. We have found a statistically significant increased frequency of D allele of PLAT TPA 25 I/D polymorphism between the entire group of patients with ONFH and controls (p=0,026, OR=1,54, CI 0,99-2,4). D allele frequency was also significantly increased in patients with primary ONFH (p=0,009, OR=1,81 CI 1,1-3,01), in males (p= 0,013; OR 1,74; 95% CIs 1,08-2,78), patients older than 50 years (p= 0,018, OR= 2,04; 95% CIs 1,09-3,82) and in cases with bilateral ONFH (p= 0,01; OR= 1,92; 95% CIs 1,13-3,27) (Table 9). The differences in DD homozygous genotype frequency were statistically significant for patients with idiopathic ONFH compared with control group (p=0,023, OR=2,75, CI 0,99-7,9) and in cases of bilateral ONFH (p=0,034; OR 3,12; 95% CIs 1,06-9,18) (Table 10). The frequencies of ID heterozygous genotype were statistically significantly higher in entire group of patients with ONFH (p=0,004 OR 2,71; 95% CIs 1,32-5,57), idiopathic ONFH (p= 0,01; OR 2,91; 95% CIs 1,24-6,87), males (p=0,0007; OR 3,75; 95% CIs 1,67-8,42), patients older than 50 years (p=0,001; OR 6,89; 95% CIs 1,87-25,84) and in cases with bilateral ONFH (p=0,009; OR 3,19; 95% CIs 1,26-8,03).

Conclusion: The results suggest that inherited hypofibrinolysis is a risk factor of idiopathic ONFH in Polish population.