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. 2024 Oct 18;25(20):11207.
doi: 10.3390/ijms252011207.

An Inexpensive and Quick Method for Genotyping of HLA Variants Included in the Spanish Pharmacogenomic Portfolio of National Health System

Irene Taladriz-Sender  1 , Gina Hernández-Osio  1 , Paula Zapata-Cobo  1 , Sara Salvador-Martín  1 , Xandra García-González  1 , Antonio Balas  2 , María Sanjurjo-Sáez  1 , Luis A López-Fernández  1
Affiliations

An Inexpensive and Quick Method for Genotyping of HLA Variants Included in the Spanish Pharmacogenomic Portfolio of National Health System

Irene Taladriz-Sender et al. Int J Mol Sci. .

Abstract

The possibility of using the same genotyping technology (TaqMan) for all the genetic tests included in the new Spanish pharmacogenomics portfolio should enable the application of a multigenotyping platform to obtain a whole pharmacogenomics profile. However, HLA-typing is usually performed with other technologies and needs to be adapted to TaqMan assays. Our aim was to establish a set of TaqMan assays for correct typing of HLA-A*31:01, HLA-B*15:02, HLA-B*57:01, and HLA-B*58:01. Therefore, we searched for and selected SNVs described in different populations as surrogate markers for these HLA alleles, designed TaqMan assays, and tested in a set of samples with known HLA-A and HLA-B. HLA-A*31:01 was correctly typed with a combination of rs1061235 and rs17179220 (PPV 100%, 95% CI 84.6-100-%; NPV 100%, 95% CI 96.5-100.0%), HLA-B*15:02 with rs10484555 (PPV 100%, 95% CI 69.2-100.0%; NPV 100%, 95% CI 96.8-100.0%) and rs144012689 (PPV 100%, 95% CI 69.2-100.0%; NPV 100%, 95% CI 96.8-100.0%), and HLA-B*57:01 with rs2395029 (PPV 99.5%, 95% CI 72.9-99.3%; NPV 99.5%, 95% CI 98.3-100.0%). HLA-B*58:01 was typed using two allele-specific TaqMan probes mixed with a ß-Globin reference and treated as a genotyping assay (PPV 100.0%, 95% CI 81.5-100.0%; NPV 100%, 95% CI 96.8-100.0%). In conclusion, we demonstrated a clinically useful way to type HLA-A and HLA-B alleles included in the Spanish pharmacogenomics portfolio using TaqMan assays.

Keywords: HLA-typing; genotyping; pharmacogenetics; pharmacogenomics.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Allelic discrimination and amplification plots for specifically designed HLA-B*58:01 assays. Carriers of HLA-B*5801 were perfectly clustered. The figure shows the results of the following: (a) the allelic discrimination plot assay for 5801A (green, HLA-B*5801 positive and ß-Globin positive; blue, HLA-B*5801 negative and ß-Globin positive); (b) the allelic discrimination plot assay for 5801B (green, HLA-B*5801 positive and ß-Globin positive; blue, HLA-B*5801 negative and ß-Globin positive); (c) the amplification plot assay for 5801A (purple, ß-Globin, orange, HLA-B*5801); and (d) the amplification plot assay for 5801B (green, ß-Globin; red, HLA-B*5801).
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