Novel genetic biomarkers for susceptibility to oral submucous fibrosis: Cytochrome P450 3A
Novel genetic biomarkers for susceptibility to oral submucous fibrosis: Cytochrome P450 3A
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口腔粘膜下纤维化易感性的新型遗传生物标志物：细胞色素 P450 3A
DOI：
10.1016/j.mehy.2011.07.049
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发表时间：
2011-11-01
影响因子：
4.7
通讯作者：
Guo, Feng
中科院分区：
文献类型：
--
作者：
Li, Ning;Hu, Qiong;Guo, Feng
口腔粘膜下纤维性变(OSF)是一种慢性隐匿性口腔黏膜疾病，具有向口腔癌转化的高风险。槟榔粉对有毒物质的药代动力学主要基于遗传易感性，咀嚼者对槟榔粉的反应存在明显的差异性。但导致OSF发育个体间差异的关键基因仍然不清楚。细胞色素P4503A(CyP3A)基因家族在内源和异源活性底物的氧化代谢中起重要作用，在不同个体中普遍发现具有不同等位基因的多态现象，被认为是药物药代动力学个体间变异的主要决定因素。根据CyP3A的特性，我们认为这种多态表达的基因可能是OSF易感性的一个预测因子。CYP 3A表达水平低的槟榔咀嚼者可能更容易受到槟榔毒性的影响，从而导致OSF损害的风险更高。同时，根据CyP3A基因某些专属区域的遗传多态可以筛选出OSF的遗传高危个体。通过分析CYP3A基因的多态性，可以区分槟榔咀嚼者的药代动力学个体间差异，从而指导OSF的治疗。(C)爱思唯尔有限公司出版的2011年。
Oral submucous fibrosis (OSF) is a chronic and insidious oral mucosal disease, which always carries high risk of transition to oral cancer. Mainly based on genetic predisposition in pharmacokinetics for toxic substances of betel quid, there are obviously variable responses to betel quid among chewers. But the key genes resulting in interindividual variability in OSF development are still obscure. The cytochrome P450 3A (CYP 3A) gene family plays major roles in the oxidative metabolism of active endogenous and xenobiotic substrates, which is generally found polymorphic with variant alleles in different individuals and regarded as a major determinant of the interindividual variability in chemicals pharmacokinetics. Based on the specific property of CYP 3A, we consider this polymorphically expressed genotype could be a predictor of OSF susceptibility. Betel-quid chewers with lower level of CYP 3A expression might be more susceptible to toxicity of betel quid, resulting in higher risk of OSF lesion. Meanwhile, individuals at genetically high risk of OSF could be screened according to the genetic polymorphisms in some exclusive regions of the CYP 3A genes. By analyzing the polymorphisms of CYP 3A genes, we could differentiate interindividual variability for pharmacokinetics of betel-quid chewers, and then guide OSF therapy. (C) 2011 Published by Elsevier Ltd.