title: 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.
abstract: 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.
authors.affiliation: Division of Medicinal Safety Science, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Maekawa
authors.forename: Jun
authors.initials: J
authors.lastname: Nishikawa
authors.forename: Nahoko
authors.initials: N
authors.lastname: Kaniwa
authors.forename: Emiko
authors.initials: E
authors.lastname: Sugiyama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Koizumi
authors.forename: Kouichi
authors.initials: K
authors.lastname: Kurose
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tohkin
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
mesh_terms: D000493:Allopurinol / Q000009:adverse effects*; D054458:Amplified Fragment Length Polymorphism Analysis; D044466:Asian People / Q000235:genetics*; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011506:Proteins / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced / Q000208:ethnology / Q000209:etiology / Q000235:genetics* / Q000276:immunology
chemical_list: D005819:Genetic Markers; D015235:HLA-B Antigens; C500126:HLA-B*58:01 antigen; C484393:PSORS1C1 protein, human; D011506:Proteins; D000493:Allopurinol