Copy number variation and incomplete linkage disequilibrium interfere with the HCP5 genotyping assay for abacavir hypersensitivity.
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.
ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah 84108, USA. roberta.melis@aruplab.com
Roberta
R
Melis
Tracy
T
Lewis
Alison
A
Millson
Elaine
E
Lyon
Gwendolyn A
GA
McMillin
Patricia R
PR
Slev
Jeffrey
J
Swensen
D056915:DNA Copy Number Variations / Q000235:genetics*; D015224:Dideoxynucleosides / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008285:Major Histocompatibility Complex / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D000099227:Abacavir
D015224:Dideoxynucleosides; D015235:HLA-B Antigens; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D000099227:Abacavir; C080521:HCP5 long noncoding RNA, human; C103707:HLA-B57 antigen