Development of a rapid and inexpensive assay for detecting a surrogate genetic polymorphism of HLA-B*58:01: a partially predictive but useful biomarker for allopurinol-related Stevens-Johnson syndrome/toxic epidermal necrolysis in Japanese.

Allopurinol-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is strongly associated with HLA-B*58:01 in various populations including Japanese. We demonstrated that several single nucleotide polymorphisms (SNPs) around the HLA region on chromosome 6 were strongly linked with HLA-B*58:01 in a previous study using Japanese allopurinol-related SJS/TEN patients. Their very strong linkage suggests that these SNPs could be used as surrogate biomarkers to find carriers of HLA-B*58:01 to avoid these serious adverse effects. In the present study, to expedite the application of this pharmacogenomic information to the proper usage of allopurinol in a clinical situation, we developed a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay for the genotyping of rs9263726 in the psoriasis susceptibility 1 candidate 1 (PSORS1C1) gene, which is in absolute linkage disequilibrium (r(2) = 1, D' = 1) with HLA-B*58:01. The developed PCR-RFLP assay using FokI restriction enzyme was able to detect three different genotypes, GG, GA, and AA of rs9263726 robustly, and thus to find HLA-B*58:01 carriers. This robust and inexpensive assay would be useful for pre-screening the subjects with HLA-B*58:01, a genetically high risk factor for allopurinol-induced SJS/TEN.

[1]  C. Sotozono,et al.  A whole-genome association study of major determinants for allopurinol-related Stevens–Johnson syndrome and toxic epidermal necrolysis in Japanese patients , 2011, The Pharmacogenomics Journal.

[2]  J Rossjohn,et al.  Rapid screening for the detection of HLA-B57 and HLA-B58 in prevention of drug hypersensitivity. , 2011, Tissue antigens.

[3]  J. Jung,et al.  Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans , 2011, Pharmacogenetics and genomics.

[4]  Chen-Yang Shen,et al.  Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. , 2011, The New England journal of medicine.

[5]  M. Aihara.  Pharmacogenetics of cutaneous adverse drug reactions , 2011, The Journal of dermatology.

[6]  Yoshiro Saito,et al.  [Current movements of four serious adverse events induced by medicinal drugs based on spontaneous reports in Japan]. , 2011, Kokuritsu Iyakuhin Shokuhin Eisei Kenkyujo hokoku = Bulletin of National Institute of Health Sciences.

[7]  Yoshiro Saito,et al.  Prediction of severe adverse drug reactions using pharmacogenetic biomarkers. , 2010, Drug metabolism and pharmacokinetics.

[8]  S. Tiamkao,et al.  Strong association between HLA-B*5801 and allopurinol-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in a Thai population , 2009, Pharmacogenetics and genomics.

[9]  C. Sotozono,et al.  HLA-B locus in Japanese patients with anti-epileptics and allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis. , 2008, Pharmacogenomics.

[10]  L. Naldi,et al.  A European study of HLA-B in Stevens–Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs , 2008, Pharmacogenetics and genomics.

[11]  S. Jee,et al.  Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions , 2006, Pharmacogenetics and genomics.

[12]  Yuan-Tsong Chen,et al.  HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[13]  L. Naldi,et al.  Correlations between clinical patterns and causes of erythema multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis: results of an international prospective study. , 2002, Archives of dermatology.

[14]  K. Tadokoro,et al.  Sequence-based association analysis of HLA class I and II alleles in Japanese supports conservation of common haplotypes , 1997, Immunogenetics.

[15]  M. Mockenhaupt,et al.  Epidemiology of erythema exsudativum multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis in Germany (1990-1992): structure and results of a population-based registry. , 1996, Journal of clinical epidemiology.

[16]  T. Juji,et al.  Report of the Japanese Central Bone Marrow Data Center. , 1996, Clinical transplants.