Abstract
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.
Highlights
A vascular necrosis of the femoral head (AVNFH) is a severe degenerative disease resulting from bone destruction, impaired microcirculation, and bone marrow adipose dystrophy [1–3]
The human VDR vitamin D receptor gene is localized on chromosome 12q12-q14
About 30 single nucleotide polymorphisms have been found in the VDR gene and can be identified by appropriate restriction endonuclease enzymes
Summary
A vascular necrosis of the femoral head (AVNFH) is a severe degenerative disease resulting from bone destruction, impaired microcirculation, and bone marrow adipose dystrophy [1–3]. These factors affect the stress bone remodeling. Determined target organ and tissue sensitivity to calcitriol, hereditary thrombophilia and hypofibrinolysis are described in the medical literature as potential causes of idiopathic types of AVNFH [7–9]. Homozygous 4G/4G variant of the plasminogen activator inhibitor gene -675 5G > 4G (rs1799889) PAI-1 was reported to be associated with a greater risk of AVNFH [16‐18]. The study of gene polymorphism that determines target organ and tissue sensitivity to calcitriol, hereditary thrombophilia and hypofibrinolysis, as molecular genetic markers of the AVNFH is important to be used as identification tool
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