Evaluation of VDR and PAI allelic genes in patients with avascular necrosis of the femoral head

Objective. To evaluate the informative value of the carrier status for allelic variations that determine the sensitivity of tissues to calcitriol (VDR) and are involved in familial thrombophilia and hypofibrinolysis (PAI-1) as molecular genetic markers of avascular necrosis of the femoral head (AVNFH).

Material and methods. A clinical and laboratory study of 300 AVNFH patients, residents of European Russia, was carried out. A comparative analysis of the alleles and genotypes frequency distribution of polymorphisms rs11568820 and rs1544410 of the VDR gene, as well as rs1799889 of the PAI-1 gene in AVNFH patients was performed.

Results. AVNFH patients showed a significant increase in the frequencies of the G/G genotype (P = 3.0E-9) and the G allele (P = 0.05) of the rs11568820 VDR polymorphism (P = 2.10E-08) as compared to controls. The frequency of the A/A genotype of the rs1544410 VDR locus in AVNFH individuals was higher than that in controls (P = 0.05).

Discussion. Carriers of the genotype G / G A-3731G (Cdx2) of the VDR gene were shown to have a 2.1-fold increased risk of developing AVNFH; carriers of the G allele appeared to have a 2.3-fold increased risk of AVNFH. The findings showed that the carriership of the 5G allele of the polymorphic locus PAI-1 -675 4G > 5G (rs1799889) is detected 1.4 times more often in AVNFH patients than in individuals from the population sample. The risk of developing the pathology is increased 2 times with the carriership of the 5G/5G genotype of this polymorphic locus.

Conclusion. Carriers of genotypes G/G rs11568820 VDR (allele G), A/A rs1544410 VDR and 5G/5G (allele 5G) at the polymorphic locus rs1799889 PAI-1 have an increased risk of developing AVNFH. This allows the use of the molecular genetic markers in the early diagnosis of AVNFH in individuals who are at greater risk for the disease.

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