Genome Sequence Variability Predicts Drug Precautions and Withdrawals from the Market.

ABSTRACT: Despite substantial premarket efforts, a significant portion of approved drugs has been withdrawn from the market for safety reasons. The deleterious impact of nonsynonymous substitutions predicted by the SIFT algorithm on structure and function of drug-related proteins was evaluated for 2504 personal genomes. Both withdrawn (n = 154) and precautionary (Beers criteria (n = 90), and US FDA pharmacogenomic biomarkers (n = 96)) drugs showed significantly lower genomic deleteriousness scores (P < 0.001) compared to others (n = 752). Furthermore, the rates of drug withdrawals and precautions correlated significantly with the deleteriousness scores of the drugs (P < 0.01); this trend was confirmed for all drugs included in the withdrawal and precaution lists by the United Nations, European Medic

SUBMITTER: Lee KH 

PROVIDER: S-EPMC5045182 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature