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- Title
Lysyl Oxidase Polymorphisms and Susceptibility to Osteosarcoma.
- Authors
Yang Liu; Bitao Lv; Zhimin He; Yujia Zhou; Carrie Han; Guodong Shi; Rui Gao; Ce Wang; Lili Yang; Haihan Song; Wen Yuan
- 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 (222G/C, 225C/G, and 473G/A) in the exons and promoter region of LOX. The 222G/C polymorphism lies in the downstream core promoter element (DPE) region and caused a decrease in promoter activity of LOX. The prevalence of the 222C 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 (222, 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 222G/C polymorphism may affect the expression of LOX, and that 222G/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.
- Subjects
LYSYL oxidase; GENETIC polymorphisms; OSTEOSARCOMA; BONE cancer; INTRONS; ELASTIN; GENE expression
- Publication
PLoS ONE, 2012, Vol 7, Issue 7, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0041610