The utility of surrogate markers in predicting HLA alleles associated with adverse drug reactions in Vietnamese
Dinh Van Nguyen,1,2,3 Janet Anderson,1 Christopher Vidal,1 Richard Fulton,1 Jamma Li,1,2,4 Suran L Fernando1,2,4
1 ImmunoRheumatology Laboratory, New South Wales Health Pathology-North, Royal North Shore Hospital, Sydney, Australia
2 Sydney Medical School-Northern, The University of Sydney, Sydney, Australia
3 Division of Allergy and Clinical Immunology, Vinmec International Hospital Times City, Hanoi, Vietnam
4 Department of Clinical Immunology and Allergy, Royal North Shore Hospital, Sydney, Australia
Abstract
Background: Screening for HLA-A31:01/HLA-B15:02, HLA-B57:01 and HLA-B58:01 is recommended in selected populations for prevention of carbamazepine, abacavir, and allopurinol-induced severe cutaneous adverse reactions (SCARs). Compared to conventional methods for detection of HLA alleles, PCR using a tag single nucleotide polymorphism (SNP) can be cost-effective, particularly where the surrogate marker SNP is in absolute linkage disequilibrium with the relevant HLA allele.
Objective: To determine guidelines for prevention of SCARs though predictive screening for the Australian Vietnamese population, the prevalence of four HLA alleles (HLA-A31:01, HLA-B15:02, HLA-B57:01 and HLA-B58:01) was examined. The utility of surrogate markers, rs2395029 and rs9263726, was investigated to predict for the presence of HLA-B57:01 and HLA-B58:01, respectively.
Methods: Genotyping for specific HLA alleles was performed in 152 healthy Vietnamese living in Sydney using validated and established PCR-based methods. SNP genotyping was conducted using restriction-fragment-length-polymorphism analysis.
Results: rs2395029 and rs9263726 strongly correlated with HLA-B57:01 (ĸ = 1, p < 0.001) and HLA-B58:01 (ĸ = 0.9, p < 0.001) with 100% sensitivity and 100% negative predictive value for predicting the HLA-B57:01 and HLA-B58:01 carriers, respectively. A high prevalence of carriers of HLA-A31:01 (3.29%), HLA-B15:02 (14.47%), HLA-B57:01 (6.58%) and HLA-B58:01 (9.21%) was revealed.
Conclusions: Screening is recommended for these alleles in Australian Vietnamese prior to introducing relevant therapies. SNPs, rs2395029 and rs9263726, can be successfully used as surrogate markers for HLA-B57:01 and HLA-B58:01 in this population.
Key words: HLA, polymorphisms, abacavir, allopurinol, carbamazepine, Toxic Epidermal Necrolysis, Stevens-Johnson syndrome, Drug Rash with Eosinophilia and Systemic Symptoms, Vietnamese,