Volume 26, Issue 10 (12-2019)
RJMS 2019, 26(10): 19-27 |
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hoseini M, sazgar H, Zia-jahromi N. Study of the effects of rs137852585 single nucleotide polymorphism existence in the Androgen Receptor (AR) encoding gene on the response to Enzalutamide treatment in patients suffering from prostate cancer.. RJMS 2019; 26 (10) :19-27
URL: http://rjms.iums.ac.ir/article-1-5506-en.html
URL: http://rjms.iums.ac.ir/article-1-5506-en.html
Shahrekord Branch, Islamic Azad University, Shahrekord, Iran , hoseinsazgar@yahoo.com
Abstract: (2773 Views)
Background: The androgen receptor belongs to the family of transcription factors of the steroid hormones receptor, and according to studies, single nucleotide mutations in the structure of this protein can affect its function and response to inhibitory drugs. In regard this purpose of this study was to investigate the effect of the single-nucleotide polymorphism rs137852585 presence in the androgen receptor-encoding gene on the response of this form to treatment with enzalutamide and to study its frequency in Iranian population.
Methods: In this case-control study, 10 ml peripheral blood was taken from 50 prostate cancer patients and 50 healthy people. Then the genomic DNA of the samples was extracted and isolated. ARMS-PCR and direct sequencing were used to determine the presence of polymorphism and the data were analyzed using SISA statistical database and Fisher's exact test. On the other hand, to evaluate the effect of mutation on the function of the androgen receptor, the Docking technique and the Autodock 4.2 software were used. Finally, determination of the allele frequency, heterozygosity and the investigation of the existence of Hardy-Weinberg equilibrium were performed using the Genepop computational server.
Results: Investigations showed that the allele frequency for rs137852585 increased for mutated allele in patients with prostate cancer (0.24) compared to healthy subjects (0.08) (p=0.003). On the other hand, reviewing the results of Docking showed that mutation in the androgen receptor structure makes enzalutamide-androgen receptor interactions thermodynamically undesirable. Demographic analyzes showed that this marker is at the Hardy-Weinberg equilibrium in the Iranian population (p>0.05).
Conclusion: The presence of single nucleotide polymorphisms induces resistance to enzalutamide by altering the active site of the androgen receptor. On the other hand, the presence of mutant allele of rs137852585 could increase prostate cancer risk.
Methods: In this case-control study, 10 ml peripheral blood was taken from 50 prostate cancer patients and 50 healthy people. Then the genomic DNA of the samples was extracted and isolated. ARMS-PCR and direct sequencing were used to determine the presence of polymorphism and the data were analyzed using SISA statistical database and Fisher's exact test. On the other hand, to evaluate the effect of mutation on the function of the androgen receptor, the Docking technique and the Autodock 4.2 software were used. Finally, determination of the allele frequency, heterozygosity and the investigation of the existence of Hardy-Weinberg equilibrium were performed using the Genepop computational server.
Results: Investigations showed that the allele frequency for rs137852585 increased for mutated allele in patients with prostate cancer (0.24) compared to healthy subjects (0.08) (p=0.003). On the other hand, reviewing the results of Docking showed that mutation in the androgen receptor structure makes enzalutamide-androgen receptor interactions thermodynamically undesirable. Demographic analyzes showed that this marker is at the Hardy-Weinberg equilibrium in the Iranian population (p>0.05).
Conclusion: The presence of single nucleotide polymorphisms induces resistance to enzalutamide by altering the active site of the androgen receptor. On the other hand, the presence of mutant allele of rs137852585 could increase prostate cancer risk.
Type of Study: Research |
Subject:
Hematology & oncology
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