About Careers MedBlog Contact us
Medindia LOGIN REGISTER
Advertisement

Rare Gene Variants Critical for Personalized Drug Treatment

by Kathy Jones on December 6, 2011 at 7:32 PM
Font : A-A+

 Rare Gene Variants Critical for Personalized Drug Treatment

Personalized medicine in future will be largely based on the use of genetic tests to predict a patient's response to drugs.

But genetic tests often only look for the most common gene variants. In a pharmacogenomics study published online today in Genome Research (www.genome.org), researchers have characterized rare genetic variants in a specific gene that can have a significant influence in disposition of a drug used to treat cancer and autoimmune disease, a finding that will help improve the effectiveness of personalized care.

Advertisement

The drug methotrexate is used to treat cancers such as acute lymphoblastic leukemia, and autoimmune diseases including rheumatoid arthritis. Common genetic variants in the SLCO1B1 gene, which encodes a transporter in the liver important for clearance of medication from the body, are present in 10-15% of the population and affect the efficiency of methotrexate clearance from the body.

Low clearance of methotrexate results in high levels in the blood and increased side effects. Rare variants could also significantly affect drug clearance, but the influence of rare versus common SLCO1B1 variants in methotrexate clearance had not yet been explored.
Advertisement

In this report, an international team of researchers sequenced the exons of SLCO1B1, the gene regions that code for protein, in a cohort of pediatric patients receiving methotrexate, finding rare genetic variants that have an effect on the efficiency of clearance of the drug from the body. "We showed that rare inherited genomic variants, present in as few as 1 in 699 people, account for a significant percentage of variability in blood levels of methotrexate," said Dr. Mary Relling of St. Jude Children's Research Hospital, senior author of the study. "This means that the high blood levels present in 2% of people are due to very rare genetic variants."

The research group then utilized computational algorithms to predict the potential negative impact of genomic variants identified in this study on function of the SLCO1B1 protein in the transport of methotrexate. They then tested these predictions in laboratory cell lines, confirming that these genetic variants conferred lower transport of the drug.

"Our discovery of important but rare coding variants in SLCO1B1 not only has implications for methotrexate, but also possibly for other drugs," explained Dr. Laura Ramsey of St. Jude Children's Research Hospital, primary author of the study. Ramsey noted that SLCO1B1 variants are tested to inform choice of the appropriate dosage of statins, commonly used to treat or prevent high cholesterol.

Ramsey added that clinical genetic tests are currently limited, generally only testing for the most common SLCO1B1 variants. "Our findings that there are additional rare functional coding variants in this gene suggest that genotyping tests would need to expand to include rare variants in order to avoid false negative test results."

Scientists from St. Jude Children's Research Hospital (Memphis, TN), Aarhus University (Aarhus, Denmark), MD Anderson Cancer Center (Houston, TX), the University of Tennessee Health Science Center (Memphis, TN), the Sidney Kimmel Comprehensive Cancer Center (Baltimore, MD), and the University of California, San Francisco (San Francisco, CA) contributed to this study.
Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
What's New on Medindia
Diet and Oral Health: The Sugary Connection May Become Sour
World AIDS Day 2022 - Equalize!
Test Your Knowledge on Sugar Intake and Oral Health
View all
Recommended Reading
News Archive
Date
Category
Advertisement
News Category

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
DNA Finger Printing Drug Toxicity Signature Drug Toxicity How Do Viruses Mutate and Why Does it Matter? 

Most Popular on Medindia

Hearing Loss Calculator Blood Pressure Calculator Sinopril (2mg) (Lacidipine) Nutam (400mg) (Piracetam) Blood - Sugar Chart Blood Donation - Recipients Selfie Addiction Calculator The Essence of Yoga Find a Doctor Loram (2 mg) (Lorazepam)
This site uses cookies to deliver our services.By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use  Ok, Got it. Close
×

Rare Gene Variants Critical for Personalized Drug Treatment Personalised Printable Document (PDF)

Please complete this form and we'll send you a personalised information that is requested

You may use this for your own reference or forward it to your friends.

Please use the information prudently. If you are not a medical doctor please remember to consult your healthcare provider as this information is not a substitute for professional advice.

Name *

Email Address *

Country *

Areas of Interests