Lysyl oxidase polymorphisms and susceptibility to osteosarcoma.
Lysyl oxidase polymorphisms and susceptibility to osteosarcoma.
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赖氨酰氧化酶多态性与骨肉瘤的易感性
DOI：
10.1371/journal.pone.0041610
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yuan W
中科院分区：
文献类型：
--
作者：
Liu Y;Lv B;He Z;Zhou Y;Han C;Shi G;Gao R;Wang C;Yang L;Song H;Yuan W
尽管骨肉瘤中存在许多遗传改变的知识，这种疾病的复杂性排除了将其生物学纳入一个简单的概念框架。赖氨酰氧化酶（LOX）催化弹性蛋白和胶原蛋白的交联，这对骨组织的结构完整性和功能至关重要。在目前的研究中，我们进行了基因组测序的所有七个外显子-包括内含子-外显子剪接位点，和LOX基因的推定的启动子区域-然后用荧光素酶报告基因分析新发现的多态性的功能。然后评估LOX多态性与骨肉瘤之间的关联。我们的测序数据揭示了LOX外显子和启动子区的三种多态性（− 22 G/C，225 C/G和473 G/A）。-22 G/C多态性位于下游核心启动子元件（DPE）区域，导致LOX启动子活性降低。与对照组相比，骨肉瘤患者中− 22 C等位基因和473 A等位基因的患病率显著增加（比值比[OR]= 3.88，95%置信区间[CI]= 1.94−7.78，p = 4.18×10−5，OR = 1.38，95%CI = 1.07−1.78，p = 0.013;经Bonferroni校正后，认为p 0.0167具有显著性）。 单倍型分析显示，Bonferroni校正后，骨肉瘤病例中CCG单倍型（-22，225，473）的频率显著高于健康对照组（p = 4.46×10−4）。 这些结果表明，-22 G/C多态性可能影响LOX的表达，-22 G/C和473 G/A多态性可能是骨肉瘤的新的危险因素。这些发现揭示了一个潜在的新途径，遗传多态性可能会影响人类疾病。
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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DOI：
10.1073/pnas.89.11.4879
发表时间：
1992-06-01
影响因子：
11.1
作者：
KRZYZOSIAK, WJ;SHINDOOKADA, N;NISHIMURA, S
通讯作者：
NISHIMURA, S
影响因子：
56.9
作者：
Kessler, E;Takahara, K;Greenspan, DS
通讯作者：
Greenspan, DS
影响因子：
4.2
作者：
Shim, H;Harris, ZL
通讯作者：
Harris, ZL
影响因子：
4.8
作者：
Gao, Song;Zhao, Yinzhi;Li, Wande
通讯作者：
Li, Wande
影响因子：
5.8
作者：
Siddikuzzaman;Grace, V. M. Berlin;Guruvayoorappan, C.
通讯作者：
Guruvayoorappan, C.