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• W2897592428 abstract "Organic anion transporting polypeptides (OATP) encoded by the SLCO gene family constitute clinically important transporters involved in the disposition of endogenous compounds and many commonly prescribed drugs, including statins, methotrexate and antihypertensive medications. Common genetic polymorphisms in SLCO genes are known to affect OATP function and modulate efficacy and safety of OATP substrates. However, current frequency data of these variants and haplotypes is generally based on few rather heterogenous populations of relatively small sample size. Furthermore, the genetic variability beyond these selected pharmacogenetic biomarkers has not been systematically analyzed. Here, we provide a global consolidated map of SLCO variability by leveraging fully compatible Next Generation Sequencing data from 138,632 unrelated individuals across seven major human populations. Overall, we find 9811 exonic single nucleotide variants and 155 copy number variations of which 99.3% were rare with frequencies <1%. Using orthogonal computational functionality predictors optimized for pharmacogenetic assessments, we find that four out of five individuals carry at least one deleterious variant in an SLCO transporter gene and rare variants contribute 23% to the genetically encoded functional variability. Moreover, 74.9% of all variants were found to be population-specific with important consequences for population-specific genotyping strategies and precision public health approaches. Combined, our analyses provide the most comprehensive data set of SLCO variability published to date and incentivize the integration of comprehensive NGS-based genotyping into personalized predictions of OATP substrate disposition." @default.
• W2897592428 created "2018-10-26" @default.
• W2897592428 creator A5045845574 @default.
• W2897592428 creator A5053109650 @default.
• W2897592428 date "2019-01-01" @default.
• W2897592428 modified "2023-10-17" @default.
• W2897592428 title "Genetic variability and population diversity of the human SLCO (OATP) transporter family" @default.
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• W2897592428 doi "https://doi.org/10.1016/j.phrs.2018.10.017" @default.
• W2897592428 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30359687" @default.
• W2897592428 hasPublicationYear "2019" @default.
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