Genome-Wide Association and Functional Studies Reveal Novel Pharmacological Mechanisms for Allopurinol.

ABSTRACT: Allopurinol, which lowers uric acid (UA) concentration, is increasingly being recognized for its benefits in cardiovascular and renal disease. However, response to allopurinol is variable. We gathered samples from 4,446 multiethnic subjects for a genome-wide association study of allopurinol response. Consistent with previous studies, we observed that the Q141K variant in ABCG2 (rs2231142), which encodes the efflux pump breast cancer resistance protein (BCRP), associated with worse response to allopurinol. However, for the first time this association reached genome-wide level significance (P = 8.06 × 10^-11 ). Additionally, we identified a novel association with a variant in GREM2 (rs1934341, P = 3.22 × 10^-6 ). In vitro studies identified oxypurinol, the active metaboli

SUBMITTER: Brackman DJ 

PROVIDER: S-EPMC6941886 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature