DNA修复基因APE1 Asp148Glu多态性与乳腺癌风险的关联
Association of DNA Repair Gene APE1 Asp148Glu Polymorphism with Breast Cancer Risk.
作者信息
AlMutairi Fatima, Pathan Akbar Ali Khan, Alanazi Mohammed, Shalaby Manal, Alabdulkarim Huda A, Alamri Abdullah, Al Naeem Abdulrahman, Elrobh Moammad, Shaik Jilani P, Khan Wajahatullah, Khan Zahid, Parine Narasimha Reddy
机构信息
Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia ; Integrated Gulf Biosystems, Riyadh 11391, Saudi Arabia.
出版信息
Dis Markers. 2015;2015:869512. doi: 10.1155/2015/869512. Epub 2015 Jul 16.
OBJECTIVE
The aim of this study was to investigate the role of APE1 Asp148Glu polymorphism in breast cancer progression in Saudi population.
METHODS
We examined the genetic variations (rs1130409) in the DNA base excision repair gene APE1 at codon 148 (Asp148Glu) and its association with breast cancer risk using genotypic assays and in silico structural as well as functional predictions. In silico structural analysis was performed with Asp148Glu allele and compared with the predicted native protein structure. The wild and mutant 3D structures of APE1 were compared and analyzed using solvent accessibility models for protein stability confirmation.
RESULTS
Genotypic analysis of APE1 (rs1130409) showed statistically significant association of Asp148Glu with elevated susceptibility to breast cancer. The in silico analysis results indicated that the nsSNP Asp148Glu may cause changes in the protein structure and is associated with breast cancer risk.
CONCLUSION
Taken together, this is the first report that established that Asp148Glu variant has structural and functional effect on the APE1 and may play an important role in breast cancer progression in Saudi population.
目的
本研究旨在调查APE1基因Asp148Glu多态性在沙特人群乳腺癌进展中的作用。
方法
我们使用基因分型检测以及计算机模拟结构和功能预测，研究了DNA碱基切除修复基因APE1第148位密码子（Asp148Glu）的基因变异（rs1130409）及其与乳腺癌风险的关联。对Asp148Glu等位基因进行了计算机模拟结构分析，并与预测的天然蛋白质结构进行比较。使用溶剂可及性模型对APE1的野生型和突变型三维结构进行比较和分析，以确认蛋白质稳定性。
结果
APE1（rs1130409）的基因分型分析显示，Asp148Glu与乳腺癌易感性升高之间存在统计学上的显著关联。计算机模拟分析结果表明，错义单核苷酸多态性Asp148Glu可能导致蛋白质结构发生变化，并与乳腺癌风险相关。
结论
综上所述，这是第一份证实Asp148Glu变异对APE1具有结构和功能影响，并可能在沙特人群乳腺癌进展中起重要作用的报告。
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