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You are here: Home / Articles / Experts Discuss the Latest Precision Medicine Research

Experts Discuss the Latest Precision Medicine Research

February 18, 2018 • By Susan Bernstein

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“Why are some patients unique and nobody seems to see their phenotypes elsewhere? Frequently, the phenotype is not loss of function. Sometimes there’s an environmental trigger,” he said. Although some patients with autoimmune disease can have an extreme presentation that makes their disease seem rare or unique, they may have family members with milder forms of the same disease. GWAS data analysis can tell us more about the many genetic variants that can affect presentation in autoimmune diseases.

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Genomics, Big Data & Therapy

GWAS data can also help refine pharmacologic therapy by clarifying how distinct patient subsets, based on their genetic or genomic profiles, might metabolize certain drugs differently, said Minoli Perera, PharmD, PhD, associate pro­fessor of pharmacology at Northwestern University Feinberg School of Medicine in Chicago, Ill. Pharmacogenetics (i.e., the genome’s role in drug response) is an increasingly important area of precision medicine, she said. Her research focuses on anti-thrombotic medications in African-American patients.

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GWAS data on warfarin have shown three genes are associated with dose requirement, which is clinically important given the tight control and therapeutic monitoring required for this drug. But these large genomic studies were performed in mostly white or Asian patient populations, she said.

“African-Americans taking warfarin, on average, require a higher dose than other patients. Known variations explained less of the variability of drug response in these patients,” she said. African-American patients on warfarin also suffer much higher rates of bleeding than other ancestry groups, “so this suggests other population-specific genetic variants may explain the dose requirement in these patients.”

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African-Americans typically have a greater genetic variation than other American populations due to their admixture of African and European ancestry, she said. “So using genotypes found in whites to guide therapy led to poor results in African-Americans. There was harm done to them if you used genotyping to determine their warfarin dose.”

Dr. Perera and her colleagues conducted the first GWAS in African-Americans to look at venous thromboembolism (VTE) risk, and they discovered a new biomarker for increased risk of the condition, thrombomodulin (THBD).14 Decreased genetic expression of THBD affects coagulation in African-American patients. They’re now studying how patients with African ancestry might metabolize drugs differently, which has widespread implications across all areas of medicine.

Challenges include developing practical ways to deliver genotyping data to clinicians, as well as access to testing and cost. “What tests will be covered by insurers? In the long run, will genotyping save money over traditional care?” she said. “We’re past the age of genotype-guided therapy. We have genomes, we have transcriptomes and we will soon have microbiomes.”

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Filed Under: Meeting Reports, Rheumatoid Arthritis, SLE (Lupus) Tagged With: ACR/ARHP Annual Meeting, Arthritis, big data, Genetic research, genomics, Lupus, Precision Medicine, Rheumatoid arthritisIssue: February 2018

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