# Translational Candidate-Gene Studies of Simvastatin-Induced Myopathy in African Americans

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $380,264

## Abstract

Project Summary/Abstract
Pharmacogenomics prescribing guidance, currently provided for more than 150 drug-gene pairs, is improving
drug efficacy and reducing adverse drug reactions for millions of Americans. However, much of this current
guidance is more relevant to Caucasians than minority patient populations. It has long been understood that
racial differences regarding the frequencies of genetic polymorphisms exist, but more recent investigations are
demonstrating that significant racial differences exist also regarding the effects resulting from those genetic
polymorphisms. This has set the stage for significant racial disparities in Pharmacogenomics and Precision
Medicine, and such disparities continue to grow as pharmacogenomics research is largely conducted in patient
populations that are predominantly or exclusively Caucasian. To reduce this disparity the National Institute on
Minority Health and Health Disparities (NIMHD) funds investigator-initiated research on health disparities, and
one focus is pharmacogenomic studies to determine medication response and optimal dosing in health
disparity populations. Candidate-gene studies in minority health populations, such as the proposed research in
this grant application, are indicated not only for the translation of newly discovered polymorphisms but also to
ensure that clinical guidance regarding pharmacogenomics testing has relevance for minority patients. Our
previous work uncovered a common functional genetic polymorphism, CYP3A4*22, to be associated with
significantly higher concentrations (nearly 3-fold increase) of simvastatin in African Americans but not in
Caucasians. Importantly, simvastatin is one of the most commonly prescribed medications, and greater
systemic exposure to simvastatin increases the likelihood of simvastatin-induced myopathy. Hundreds of
thousands of the approximate 10 million African Americans prescribed simvastatin on an annual basis are
carriers of at least one copy of the CYP3A4*22 polymorphism and therefore are likely at a significantly
increased risk of simvastatin-induced myopathy. This increased risk could potentially be readily mitigated by a
prescribed lower dose, alternate statin type or alternate lipid-lowering strategy. The basic science, translational
and clinical investigations proposed in this grant provide the evidence needed to potentially translate this into
clinical practice. Specifically, in vitro molecular genetics studies of liver tissue (predominant site of CYP3A4
metabolism) will be performed to better characterize the extent and mechanisms underlying the decrease of
CYP3A4 metabolism associated with CYP3A4*22 in African Americans as well as to potentially elucidate any
additional polymorphisms in CYP3A4 relevant to African Americans. The proposed clinical investigation will
compare daily simvastatin systemic exposure in African American CYP3A4*22 carriers and non-carriers,
providing better quantification of the increased simvastatin exposur...

## Key facts

- **NIH application ID:** 9899310
- **Project number:** 5R01MD011307-04
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Sakima Ahmad Smith
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $380,264
- **Award type:** 5
- **Project period:** 2017-09-24 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899310

## Citation

> US National Institutes of Health, RePORTER application 9899310, Translational Candidate-Gene Studies of Simvastatin-Induced Myopathy in African Americans (5R01MD011307-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9899310. Licensed CC0.

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