Association between PARP-1 V762A polymorphism and breast cancer susceptibility in Saudi population

PLoS One. 2013 Dec 31;8(12):e85541. doi: 10.1371/journal.pone.0085541. eCollection 2013.

Abstract

Genetic aberrations of DNA repair enzymes are known to be common events and to be associated with different cancer entities. Aim of the following study was to analyze the genetic association of rs1136410 (Val762Ala) in PARP1 gene with the risk of breast cancer using genotypic assays and insilico structural predictions. Genotypic analysis of individual locus showed statistically significant association of Val762Ala with increased susceptibility to breast cancer. Protein structural analysis was performed with Val762Ala variant allele and compared with the predicted native protein structure. Protein prediction analysis showed that this nsSNP may cause changes in the protein structure and it is associated with the disease. In addition to the native and mutant 3D structures of PARP1 were also analyzed using solvent accessibility models for further protein stability confirmation. Taken together, this the first study that confirmed Val762Ala variant has functional effect and structural impact on the PARP1 and may play an important role in breast cancer progression in Saudi population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Asian People / genetics*
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Computer Simulation
  • Enzyme Stability
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Molecular Dynamics Simulation
  • Mutation
  • Neoplasm Staging
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / chemistry
  • Poly(ADP-ribose) Polymerases / genetics*
  • Polymorphism, Single Nucleotide*
  • Saudi Arabia

Substances

  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases

Grants and funding

This study was financially supported by a grant from National Science, Technology, and Innovation Plan strategic technologies program number 10-BIO897-2 in the Kingdom. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.