Low-frequency variants at the CYP2C9 locus among Puerto Rican patients on warfarin: in silico predictions of functionality and conservation.

ABSTRACT: Aim: Perform in silico predictions of functional consequences of CYP2C9 variants identified by next-generation sequencing in Puerto Ricans. Methods: Identified low-frequency CYP2C9 variants (minor allele frequencies <2%) were evaluated using the Combined Annotation-Dependent Depletion (CADD v1.3) tools and molecular modeling/docking analysis to predict impact on CYP2C9 activity. Results: CYP2C9*5,*8,*9,*11,*12,*21 and a novel *61 induce conformational changes that affect the binding site of S-warfarin. Most of these deleterious variants occur at higher frequency among individuals with large African ancestry. Conclusion: The unfavorable distance of S-warfarin from heme group, and low-bin

SUBMITTER: Claudio-Campos K 

PROVIDER: S-EPMC6739902 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature