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口腔鳞状细胞癌患者 CYP2C9 多态性及其在改变苯并[a]芘代谢中的作用。

CYP2 C9 polymorphism among patients with oral squamous cell carcinoma and its role in altering the metabolism of benzo[a]pyrene.

机构信息

Senior Lecturer, Oral and Maxillofacial Pathology and Microbiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India.

Professor and Head of the Department, Department of Oral and Maxillofacial Pathology and Microbiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India.

出版信息

Oral Surg Oral Med Oral Pathol Oral Radiol. 2020 Sep;130(3):306-312. doi: 10.1016/j.oooo.2020.06.021. Epub 2020 Jul 4.

Abstract

OBJECTIVES

The aim of this study was to evaluate the prevalence of CYP2 C9 polymorphism among healthy controls and patients with oral squamous cell carcinoma (OSCC) and to analyze the risk of disease development. We also investigated the interaction between CYP2 C9 wild type and the polymorphic variants with benzo[a]pyrene by using molecular docking analysis.

STUDY DESIGN

The study included 46 patients with OSCC and 46 controls. Amplification of the genomic DNA was done by using allele-specific polymerase chain reaction and then analyzed by using agarose gel electrophoresis. Molecular docking was then carried out to determine the interaction of CYP2 C91, CYP2 C92, and CYP2 C9*3 with benzo[a]pyrene.

RESULTS

In the OSCC group, CYP2 C92 and CYP2 C93 polymorphisms were 17.4% and 15.2%, respectively, and in the control group, they were 8.7% and 6.5%, respectively. The OSCC group showed a statistically significant (P = .043) increase in the prevalence of CYP2 C9 polymorphic variants compared with the control group. The docking analysis showed benzo[a]pyrene to bind specifically to the altered single nucleotide catalytic site in the polymorphic CYP2 C9*3 enzyme.

CONCLUSIONS

This study demonstrates that functionally important CYP2 C9 polymorphism exists among patients with OSCC, with a modest increase in the risk of disease development in those individuals who acquire these poor metabolizing variants. The modified docking of CYP2 C9*3 with benzo[a]pyrene signifies altered metabolism in vivo.

摘要

目的

本研究旨在评估 CYP2 C9 多态性在健康对照者和口腔鳞状细胞癌(OSCC)患者中的流行率,并分析疾病发展的风险。我们还通过分子对接分析研究了 CYP2 C9 野生型与多态变异型与苯并[a]芘之间的相互作用。

设计

本研究纳入了 46 例 OSCC 患者和 46 例对照者。通过等位基因特异性聚合酶链反应扩增基因组 DNA,然后通过琼脂糖凝胶电泳进行分析。然后进行分子对接以确定 CYP2 C91、CYP2 C92 和 CYP2 C9*3 与苯并[a]芘的相互作用。

结果

在 OSCC 组中,CYP2 C92 和 CYP2 C93 多态性分别为 17.4%和 15.2%,而在对照组中分别为 8.7%和 6.5%。与对照组相比,OSCC 组 CYP2 C9 多态性变异的流行率具有统计学显著差异(P =.043)。对接分析表明,苯并[a]芘特异性结合在多态 CYP2 C9*3 酶的改变单核苷酸催化位点上。

结论

本研究表明,OSCC 患者中存在功能重要的 CYP2 C9 多态性,在那些获得这些不良代谢变异体的个体中,疾病发展的风险适度增加。CYP2 C9*3 与苯并[a]芘的修饰对接表明体内代谢的改变。

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