alexa Copy number variation and incomplete linkage disequilibrium interfere with the HCP5 genotyping assay for abacavir hypersensitivity.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Pharmacogenomics & Pharmacoproteomics

Author(s): Melis R, Lewis T, Millson A, Lyon E, McMillin GA,

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Abstract Carriers of HLA-B*57:01 are at risk for Abacavir hypersensitivity reaction (ABC-HSR). In Caucasians, a SNP (rs2395029) in the HCP5 gene is reported to be in linkage disequilibrium (LD) with HLA-B*57:01. Genotyping the HCP5 SNP has increasingly been adopted as a simple method to screen for susceptibility to ABC-HSR. We genotyped both the HCP5 SNP and HLA-B*57:01 in a set of 1888 samples and found a good correlation; significantly, however, one HLA-B*57:01-positive sample tested negative for the HCP5 SNP. In addition, HCP5 could not be amplified in two samples, both negative for HLA-B*57:01. Further investigation demonstrated both samples were homozygous for deletion of the HCP5 gene. The fact HCP5 occurs within a region of copy number variation and the fact LD is incomplete and may vary between ethnicities should be considered when using the HCP5 SNP as a surrogate marker for HLA-B*57:01. This article was published in Genet Test Mol Biomarkers and referenced in Journal of Pharmacogenomics & Pharmacoproteomics

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