Abstract 403: Analysis of the functional consequences of single nucleotide polymorphisms in CYP3A4 gene to prostate cancer in men of African ancestry

Prostate cancer (CaP) is the leading cause of cancer death among Black men and its pathogenesis is linked to testosterone metabolism. CYP3A4 deactivates testosterone and the polymorphisms of its gene are known to alter testosterone metabolism. In this study, computational techniques were used to investigate the effects of nonsynonymous single nucleotide polymorphisms (nsSNPs) in the CYP3A4 gene in African Americans exome sequence. A case-control study was also carried out on 100 prostate cancer patients and 100 controls, among Yoruba men in Nigeria, to investigate the allelic variants of CYP3A4*1B (rs2740574 A>G) using polymerase chain reaction restriction fragment length polymorphism. A total of 22 nsSNPs were found in CYP3A4 gene of African American; out of which, 13 mutations (Q472R, M445T, K421R, R403C, I396T, L373F, R372I, I335T, T309I, V191A, D174H, R162W and S134C) were predicted to have deleterious effects on the CYP3A4 protein. The protein structural analysis of these amino acid variants revealed that M445T mutation could result in an increased free energy with a significant (p