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. 2015:2015:869512.
doi: 10.1155/2015/869512. Epub 2015 Jul 16.

Association of DNA Repair Gene APE1 Asp148Glu Polymorphism with Breast Cancer Risk

Fatima AlMutairi  1 , Akbar Ali Khan Pathan  2 , Mohammed Alanazi  1 , Manal Shalaby  3 , Huda A Alabdulkarim  4 , Abdullah Alamri  1 , Abdulrahman Al Naeem  5 , Moammad Elrobh  1 , Jilani P Shaik  1 , Wajahatullah Khan  6 , Zahid Khan  1 , Narasimha Reddy Parine  1
Affiliations

Association of DNA Repair Gene APE1 Asp148Glu Polymorphism with Breast Cancer Risk

Fatima AlMutairi et al. Dis Markers. 2015.

Abstract

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.

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Figures

Figure 1
Figure 1
Schematic structure of the wild-type and mutant (Asp148Glu) amino acid.
Figure 2
Figure 2
Stability change of the mutant calculated by ProSA server.
Figure 3
Figure 3
(a) Ribbon diagram of APE1 protein showing all the three side chains A, B, and C. (b) APE1 structure superimposed with wild-type and mutant residue with mutation Asp148Glu enlarged. (c) Molecular dynamics (MD) simulation showing truncated octahedron boundary explicit water solvated and hydrogen atoms. The visual inspection also allows identifying the side chain of Glu residues involved in hydrogen bonding with the surrounding molecules.
See this image and copyright information in PMC

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