A team of researchers led by Prof Liu Jianjun from A*STAR’s Genome Institute of Singapore (GIS) has discovered that the presence of a gene allele known as HLA-B*13:01 could cause a severe adverse drug reaction (ADR) to dapsone, which could be fatal. The important discovery will lead to the development of HLA-B*13:01-based diagnostic tests, which will identify high-risk individuals of this potentially life-threatening condition, and help improve the safety of dapsone therapy.
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% of individuals treated with dapsone develop a severe adverse drug reaction known as dapsone hypersensitivity syndrome (DHS) and between 11% and 13% die as a result. This is alarming as no test is currently available to predict the risk of DHS in patients.
Prof Liu, Senior Group Leader of Human Genetics and Deputy Director of Research Programmes at the GIS, and his colleagues performed a genome-wide association study on 76 DHS patients and 1,304 controls, and discovered that the presence of a particular HLA-B molecule (called HLA-B*13:01) 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 times 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% 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.
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