Association of the genetic marker for abacavir hypersensitivity HLA-B*5701 with HCP5 rs2395029 in Mexican Mestizos

Pharmacogenomics. 2011 Jun;12(6):809-14. doi: 10.2217/pgs.11.31. Epub 2011 Apr 21.

Abstract

Prospective screening for HLA-B*5701 decreases or abolishes abacavir hypersensitivity reaction. In Caucasians, the HLA complex protein 5 gene (HCP5) rs2395029(G) allele is in complete linkage disequilibrium (LD) with HLA-B*5701 (r(2) = 1).

Aim: To assess the frequency of HLA-B*5701 and its LD with HCP5 rs2395029(G) allele, to extend our knowledge of genetic variants that are of critical relevance for the development of pharmacogenetics in Mexico.

Materials & methods: We genotyped 300 Mexican Mestizos from the Mexican Genome Diversity Project. HLA-B*5701 genotyping was performed using a DNA sequencing method. HCP5 rs2395029 was genotyped using a custom TaqMan(®) SNP genotyping assay and confirmed by direct sequencing. Genotypes for 14 SNPs in the HCP5 region were retrieved from the Mexican Genome Diversity Project database for LD analysis.

Results: HLA-B*5701 carrier frequency was 2% and the allelic frequency was 0.010. Haplotype analysis revealed that HLA-B*5701 and the HCP5 rs2395029(G) allele are in complete LD (r(2) = 1) in this Mexican Mestizos sample.

Conclusion: It is feasible to have a pharmacogenetic program based on HCP5 rs2395029 genotyping as a screening tool with confirmation of HLA-B*5701 carriage by sequenciation, to prevent abacavir hypersensitivity reaction in Mexican patients before initiating abacavir therapy.

MeSH terms

  • Alleles
  • Dideoxynucleosides / adverse effects*
  • Dideoxynucleosides / therapeutic use
  • Drug Hypersensitivity / genetics*
  • Drug Hypersensitivity / immunology
  • Gene Frequency
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease
  • HLA-B Antigens / genetics*
  • HLA-B Antigens / immunology
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Major Histocompatibility Complex / genetics*
  • Major Histocompatibility Complex / immunology
  • Mexico
  • Pharmacogenetics
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Reverse Transcriptase Inhibitors / adverse effects*
  • Reverse Transcriptase Inhibitors / therapeutic use

Substances

  • Dideoxynucleosides
  • Genetic Markers
  • HCP5 long noncoding RNA, human
  • HLA-B Antigens
  • HLA-B*57:01 antigen
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Reverse Transcriptase Inhibitors
  • abacavir