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  • Title: Plasminogen activator inhibitor-1 promoter sequence variations in idiopathic osteonecrosis of head of femur.
    Author: Raman S, Dada R, Nag TC, Yadav CS.
    Journal: Indian J Med Res; 2021 Jun; 154(6):849-856. PubMed ID: 35662090.
    Abstract:
    BACKGROUND & OBJECTIVES: Primary or idiopathic osteonecrosis of femur head (ONFH) is the second most commonly observed cause among Indian patients suffering from ischemic ONFH. Although a number of genetic polymorphisms have been associated with idiopathic ONFH pathogenesis in Korean and Chinese populations, there are no studies in the Indian population. This is an exploratory study designed to implicate in promoter sequence polymorphisms of a critical fibrinolytic system regulator, plasminogen activator inhibitor-1 (PAI-1) gene, in cases of idiopathic osteonecrosis. Promoter sequence variations can affect expression levels of PAI-1 gene and may disrupt the coagulation/fibrinolytic equilibrium, which may finally culminate into osteonecrosis. Hence, the aim of the study was to investigate the role of single-nucleotide polymorphisms (SNPs) in the promoter region of PAI-1 gene and osteonecrosis development. METHODS: Two SNPs of the PAI-1 gene (rs2227631, -844 G/A; rs1799889, -675 4G/5G) were genotyped in 25 patients diagnosed with idiopathic ONFH and 25 control subjects, using direct sequencing. Subsequently, association analyses were performed for the genotyped SNPs. RESULTS: Both the rs2227631 and rs1799889 genotype and allele frequencies of PAI-1 gene showed an insignificant association with osteonecrosis risk (P=0.717, 0.149). Haplotype frequencies of rs2227631 and rs1799889 were also calculated in patients having idiopathic ONFH and controls. Although the distribution of haplotype GA-4G 4G was found to be the highest among the cases, it was not significantly different when compared with the controls. INTERPRETATION & CONCLUSIONS: Our findings demonstrate that the minor alleles of promoter region sequences of the PAI-1 gene do not contribute to an increase in ONFH predisposition. However, this is a preliminary study and its findings should be considered as suggestive for studies to be done in a larger sample size.
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