Association of the genetic marker for abacavir hypersensitivity HLA-B*5701 with HCP5 rs2395029 in Mexican Mestizos.
نویسندگان
چکیده
UNLABELLED 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.
منابع مشابه
Use of the HCP5 single nucleotide polymorphism to predict hypersensitivity reactions to abacavir: correlation with HLA-B*5701.
OBJECTIVES To study the correlation between the HLA-B*5701 allele and the single nucleotide polymorphism in HCP5 (rs2395029). PATIENTS AND METHODS All HIV patients naive for abacavir seen at our institution between September 2007 and December 2008 were prospectively screened for HLA-B*5701. HCP5 rs2395029 genotyping was carried out by allelic discrimination using the TaqMan 5'-nuclease assay....
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The HLA-B 5701 allele is predictive of hypersensitivity reaction to abacavir, a response herein termed "ABC-HSR." This study of 1,103 individuals infected with human immunodeficiency virus assessed the usefulness of genotyping a HCP5 single-nucleotide polymorphism (SNP), rs2395029, in relation to ABC-HSR. In populations with European ancestry, rs2395029 is in linkage disequilibrium with HLA-B 5...
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Abacavir hypersensitivity reaction (ABC-HSR) is associated with the presence of HLA-B*5701 allele. Alternative tests for ABC-HSR associated allele determination are needed where sequence-based HLA typing is not available, particularly in resource-limited settings or developing countries. This study focused on the development and evaluation of two HLA-B*5701 tagging SNPs (single nucleotide polym...
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BACKGROUND The use of abacavir--a potent HIV-1 nucleoside-analogue reverse-transcriptase inhibitor--is complicated by a potentially life-threatening hypersensitivity syndrome in about 5% of cases. Genetic factors influencing the immune response to abacavir might confer susceptibility. We aimed to find associations between MHC alleles and abacavir hypersensitivity in HIV-1-positive individuals t...
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ورودعنوان ژورنال:
- Pharmacogenomics
دوره 12 6 شماره
صفحات -
تاریخ انتشار 2011