Comparison between the<i>HLA-B</i><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:msup><mml:mrow/><mml:mrow><mml:mo>∗</mml:mo></mml:mrow></mml:msup></mml:math><i>58 : 01</i>Allele and Single-Nucleotide Polymorphisms in Chromosome 6 for Prediction of Allopurinol-Induced Severe Cutaneous Adverse Reactions

Abstract

Severe cutaneous adverse drug reactions (SCARs) are life-threatening reactions. The strong association between the <i>HLA-B</i>^∗<i>58 : 01</i> allele and allopurinol-induced SCARs is well recognized. Screening for <i>HLA-B</i>^∗<i>58 : 01</i> allele before prescribing allopurinol in some populations has been recommended. Several single-nucleotide polymorphisms (SNPs) in chromosome 6 have been found to be tightly linked with the <i>HLA</i> allele, and these SNPs have been proposed as surrogate markers of the <i>HLA-B</i>^∗<i>58 : 01</i> allele. This study aimed to evaluate the association between three SNPs in chromosome 6 and allopurinol-induced SCARs in a Thai population. The linkage disequilibrium between the <i>HLA-B</i>^∗<i>58 : 01</i> allele and these SNPs was also evaluated. Results showed that three SNPs including rs9263726, rs2734583, and rs3099844 were significantly associated with allopurinol-induced SCARs but with a lower degree of association when compared with the <i>HLA-B</i>^∗<i>58 : 01</i> allele. The sensitivity, specificity, PPV, and NPV of these SNPs were comparable to those of the <i>HLA-B</i>^∗<i>58 : 01</i> allele. Although detection of the SNP is simpler and less expensive compared with that of the <i>HLA-B</i>^∗<i>58 : 01</i> allele, these SNPs were not perfectly linked with the <i>HLA-B</i>^∗<i>58 : 01</i> allele. Screening using these SNPs as surrogate markers of the <i>HLA-B</i>^∗<i>58 : 01</i> allele to avoid SCARs prior to allopurinol administration needs caution because of their imperfect linkage with the <i>HLA-B</i>^∗<i>58 : 01</i> allele.