Lysyl Oxidase Polymorphisms and Susceptibility to Osteosarcoma
Open Access
- 23 July 2012
- journal article
- retracted article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (7), e41610
- https://doi.org/10.1371/journal.pone.0041610
Abstract
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.This publication has 31 references indexed in Scilit:
- Lysyl Oxidase G473A Polymorphism Is Associated with Increased Risk of Coronary Artery DiseasesDNA and Cell Biology, 2011
- Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literatureClinical & Experimental Metastasis, 2011
- A Loss-of-Function Polymorphism in the Propeptide Domain of the LOX Gene and Breast CancerCancer Research, 2009
- Lysyl Oxidase (Lox) Gene Deficiency Affects Osteoblastic PhenotypeCalcified Tissue International, 2009
- Cloning and Characterization of the Rat Lysyl Oxidase Gene PromoterOnline Journal of Public Health Informatics, 2007
- Matrix Proteins and Mineralization: An OverviewConnective Tissue Research, 1996
- Quantitative Polymerase Chain Reaction of Lysyl Oxidase mRNA in Malignantly Transformed Human Cell Lines Demonstrates That Their Low Lysyl Oxidase Activity Is Due to Low Quantities of Its mRNA and Low Levels of Transcription of the Respective GeneOnline Journal of Public Health Informatics, 1995
- COLLAGENS: Molecular Biology, Diseases, and Potentials for TherapyAnnual Review of Biochemistry, 1995
- Deficient production of lysyi oxidase in cultures of malignantly transformed human cellsFEBS Letters, 1986
- Promoter Sequences of Eukaryotic Protein-Coding GenesScience, 1980