Lysyl oxidase polymorphisms and susceptibility to osteosarcoma.

• Main Authors: Yang Liu, Bitao Lv, Zhimin He, Yujia Zhou, Carrie Han, Guodong Shi, Rui Gao, Ce Wang, Lili Yang, Haihan Song, Wen Yuan
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2012-01-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC3402457?pdf=render

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.