The variation of mitochondrial NADH dehydrogenase subunit 4 (mtND4) and molecular dynamics simulation of SNPs among Iranian women with breast cancer

• Published in: Journal of molecular graphics & modelling 2018-10, Vol.85, p.242-249
• Main Authors: Arezi, Parastoo, Rezvani, Zahra
• Format: Article
• Language: English
• Subjects: Breast cancer; Genetic changes; Iran; mtND4; Protein structure change
• ISSN: 1093-3263; 1873-4243
• DOI: 10.1016/j.jmgm.2018.08.011

Breast cancer is the second cause of death among women all around the world. One out of every eight women is diagnosed with breast cancer in Iran. There are many reasons for cancer, one of which is the mutations in the mitochondrial genome observed in most breast cancer studies. However, the aim of this study is to evaluate the genetic region of NADH dehydrogenase subunit 4 in patients with breast cancer. First, the genomic DNA was extracted from a tissue. The NADH dehydrogenase subunit 4 coding region was amplified by PCR, and then the SSCP was sequenced. After that, the molecular dynamics were employed. The association between the mutations and the prognostic factors such as ER, PR, HER-2, and age were statistically examined. The sequence of the ND4 area was determined in 24 suspected patients, and 15 nucleotide changes were reported. The role of this variations was investigated by in-silico. The harmful mutations were predicted based on some servers. The molecular dynamics results showed that there is a significant relationship between the mutant protein and the changes in the structural conformation. Our results showed that the mutation in the ND4 area plays an important role in developing breast cancer. So, it can be concluded that the mitochondrial NADH dehydrogenase analysis may help to detect breast cancer in the early stages. [Display omitted] •The human mitochondrial genome-encoded 13 proteins of the respiratory chain, 22 tRNAs and 2 mRNAs. ND4 (11860-11646) is one of the subunits of the respiratory chain.•The sequence of mtND4 in 24 suspected patients was determined and 15 nucleotide changes were reported.•Molecular dynamics were carried out for 2 harmful variations and results show that this variation effect on protein structure.•Statistical analysis shows there was no relation between ND4 mutations and clinicopathological information.