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.

Download Full-text

Molecular genetic markers for thyroid FNAB

Nuklearmedizin ◽

10.1055/s-0037-1616610 ◽

2015 ◽

Vol 54 (03) ◽

pp. 94-100 ◽

Cited By ~ 4

Author(s):

P. B. Musholt ◽

T. J. Musholt

Keyword(s):

Genetic Markers ◽

Thyroid Nodules ◽

Molecular Genetic ◽

Genetic Alterations ◽

Diagnostic Tools ◽

Ultrasound Screening ◽

Thyroid Malignancy ◽

Thyroid Carcinomas ◽

Molecular Genetic Markers ◽

The Impact

SummaryAim: Thyroid nodules > 1 cm are observed in about 12% of unselected adult employees aged 18–65 years screened by ultrasound scan (40). While intensive ultrasound screening leads to early detection of thyroid diseases, the determination of benign or malignant behaviour remains uncertain and may trigger anxieties in many patients and their physicians. A considerable number of thyroid resections are consecutively performed due to suspicion of malignancy in the detected nodes. Fine needle aspiration biopsy (FNAB) has been recommended for the assessment of thyroid nodules to facilitate detection of thyroid carcinomas but also to rule out malignancy and thereby avoid unnecessary thyroid resections. However, cytology results are dependent on experience of the respective cytologist and unfortunately inconclusive in many cases. Methods: Molecular genetic markers are already used nowadays to enhance sensitivity and specificity of FNAB cytology in some centers in Germany. The most clinically relevant molecular genetic markers as pre-operative diagnostic tools and the clinical implications for the intraoperative and postoperative management were reviewed. Results: Molecular genetic markers predominantly focus on the preoperative detection of thyroid malignancies rather than the exclusion of thyroid carcinomas. While some centers routinely assess FNABs, other centers concentrate on FNABs with cytology results of follicular neoplasia or suspicion of thyroid carcinoma. Predominantly mutations of BRAF, RET/PTC, RAS, and PAX8/PPARγ or expression of miRNAs are analyzed. However, only the detection of BRAF mutations predicts the presence of (papillary) thyroid malignancy with almost 98% probability, indicating necessity of oncologic thyroid resections irrespective of the cytology result. Other genetic alterations are associated with thyroid malignancy with varying frequency and achieve less impact on the clinical management. Conclusion: Molecular genetic analysis of FNABs is increasingly performed in Germany. Standardization, quality controls, and validation of various methods need to be implemented in the near future to be able to compare the results. With increasing knowledge about the impact of genetic alterations on the prognosis of thyroid carcinomas, recommendations have to be defined that may lead to individually optimized treatment strategies.

Download Full-text