Lysyl Oxidase Polymorphisms and Susceptibility to Osteosarcoma
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Dossier post-publication
- Nature
- Retraction
- Motif
- Compromised Peer Review;
- Date
- 9/29/2022 0:00
- Signalé par OpenAlex ?
- Oui
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Résumé
Despite the knowledge of many genetic alterations present in osteosarcoma, the complexity of this disease precludes placing its biology into a simple conceptual framework. Lysyl oxidase (LOX) catalyzes the cross-linking of elastin and collagen, which is essential for the structural integrity and function of bone tissue. In the current study, we performed genomic sequencing on all seven exons--including the intron-exon splice sites, and the putative promoter region of LOX gene--followed by luciferase reporter assay to analyze the function of newly identified polymorphisms. Associations between LOX polymorphisms and osteosarcoma were then evaluated. Our sequencing data revealed three polymorphisms (-22G/C, 225C/G, and 473G/A) in the exons and promoter region of LOX. The -22G/C polymorphism lies in the downstream core promoter element (DPE) region and caused a decrease in promoter activity of LOX. The prevalence of the -22C allele and 473A allele were significantly increased in osteosarcoma patients compared to controls (odds ratio [OR] = 3.88, 95% confidence interval [CI]= 1.94-7.78, p = 4.18×10(-5), and OR = 1.38, 95%CI = 1.07-1.78, p = 0.013; p 0.0167 was considered significant after Bonferroni correction). Analyzing haplotype showed that the frequency of CCG haplotype (-22, 225, 473) was significantly higher in osteosarcoma cases than in healthy controls after Bonferroni correction (p = 4.46×10(-4)). These results indicate that the -22G/C polymorphism may affect the expression of LOX, and that -22G/C and 473G/A polymorphisms may be new risk factors for osteosarcoma. These findings reveal a potential new pathway by which genetic polymorphisms may affect human diseases.
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La notice
- Revue
- PLoS ONE
- Thématique
- Microbial metabolism and enzyme function
- Domaine
- Biochemistry, Genetics and Molecular Biology
- Établissements canadiens
- University of TorontoWestern University
- Organismes subventionnaires
- National Natural Science Foundation of China
- Mots-clés
- Lysyl oxidaseHaplotypeOsteosarcomaExonAlleleOdds ratioGeneticsBiologyPromoterSingle-nucleotide polymorphismGenotypeMolecular biologyElastinCancer researchGeneMedicineInternal medicineGene expression
- Résumé présent dans OpenAlex
- oui