Open AccessLysyl Oxidase Polymorphisms and Susceptibility to Osteosarcoma
Author(s) -
Yang Liu,
Bitao Lv,
Zuming He,
Y. Zhou,
Carrie Han,
Guodong Shi,
Rui Gao,
Ce Wang,
Lili Yang,
Haihan Song,
Wen Yuan
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0041610
Subject(s) - lysyl oxidase , haplotype , exon , osteosarcoma , allele , genetics , biology , odds ratio , promoter , single nucleotide polymorphism , microbiology and biotechnology , genotype , elastin , cancer research , gene , medicine , gene expression , extracellular matrix
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.