Scientists Discover Gene Linked To Fatal Drug Allergy

Researchers have discovered that a gene allele known as HLA-B*13:01 could cause a severe drug reaction to dapsone, commonly prescribed for the treatment of leprosy.

AsianScientist (Oct. 24, 2013) – A team of researchers from Singapore and China has discovered that the presence of a gene allele known as HLA-B*13:01 could cause an adverse drug reaction to dapsone, commonly prescribed for the treatment of leprosy.

The study was led by Prof. Liu Jianjun from the A*STAR Genome Institute of Singapore (GIS) and published this week in the New England Journal of Medicine.

Dapsone (diamino-diphenyl sulfone) is a drug used in the treatment of various forms of infectious and inflammatory diseases and is commonly prescribed for the treatment of leprosy. Up to 3.6 percent of individuals treated with dapsone develop a severe adverse drug reaction known as dapsone hypersensitivity syndrome (DHS) and between 11 and 13 percent die as a result. This is alarming as no test is currently available to predict the risk of DHS in patients.

Liu and his colleagues performed a genome-wide association study on 76 DHS patients and 1,304 controls, and discovered that the presence of the HLA-B*13:01 allele increased the risk of DHS. Individuals carrying a single copy of HLA-B*13:01 run 34 times the risk of being hit by DHS as compared to those who do not carry this allele . The scientists further found that the risk is magnified 100 fold for those who carry two copies of HLA-B*13:01.

This study also showed that the allele HLA-B*13:01 has a sensitivity and specificity of above 85 percent in predicting the risk of DHS. Additionally, the implementation of HLA-B*13:01-based diagnostic testing reduces the risk of DHS by an impressive seven-fold.

“This is an excellent testimony that human genetic studies are a powerful tool to discover novel biomarkers and biological insight into disease development as well as adverse drug reactions. Genetic studies of ADR can help to improve the safety of drug treatment. However, ADRs are very much understudied, particularly in the Asian population. More such studies of ADRs are needed,” said Liu.

According to co-lead author Prof. Furen Zhang, Director of the Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Science, China, the discovery of the HLA-B1301 allele as a risk factor for DHS may lead to the development of a clinical test kit to identify high-risk individuals of this potentially fatal condition.

The article can be found at: Zhang F-R et al. (2013) HLA-B*13:01 and Dapsone-Induced Hypersensitivity Syndrome.


Source: A*STAR.
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