The allele frequency of HLA-B*5801 has been reported to be as high as 6–8% among Southeast Asian populations, and <1% among Western European populations, respectively.[7, 8] In their study, Hung et al.[9] used a case-control association study in the Han Chinese in Taiwan, to identify genetic markers for allopurinol-induced severe cutaneous adverse reactions (allopurinol-SCAR). Allopurinol-SCAR

included the drug hypersensitivity syndrome, SJS and TEN. They used two groups of controls, the first being 135 patients who had been on allopurinol for at least 6 months without adverse events, and a second control group of 93 subjects from the general population. They found that all 51 patients (100%) with allopurinol-SCAR carried the HLA-B*5801 gene. The presence of chronic renal insufficiency also increased the risk of developing PLX-4720 clinical trial allopurinol-SCAR MAPK Inhibitor Library supplier (odds ratio 4.7; confidence interval [CI] 2.3–9.3). Tassaneeyakul[10] and Kaniwa[11] found a strong association

between HLA-B*5801 and allopurinol-related SJS and TEN in Thai (100%) and Japanese (4/5) patients, respectively. Kang[12] studied 25 Korean patients with allopurinol-SCAR and found a HLA-B*5801 frequency of 92% in these patients versus 10.5% in controls. Furthermore, Jung[13] discovered that the incidence of allopurinol-SCAR in Korean patients with chronic renal insufficiency was considerably higher if they also carried the HLA-B*5801 gene.

In fact, the association between HLA-B*5801 allele and allopurinol-SCAR has been found to be consistent across different populations, both Asian and non-Asian.[14] A major limitation of individual studies arises from the low incidence of allopurinol-SCAR, which results in observational studies with small sample sizes and insufficient power. Somkrua and colleagues performed a systematic review and meta-analysis in order to accumulate and quantitatively analyze the genetic association between HLA-B*5801 and allopurinol-induced SJS/TEN as well as to elucidate any between-study heterogeneity.[15] They next analyzed four studies which included 55 SJS/TEN cases and 678 matched controls (allopurinol-tolerant control) and five studies with 69 SJS/TEN cases and 3378 population controls (general population). They concluded that allopurinol users with HLA-B*5801 have a 80–97 times increased risk of developing SJS/TEN compared to those who do not have this gene. Furthermore, sensitivity analyses suggested that the summary odds ratios remained significant regardless of populations, thus highlighting the potential of genotyping in different populations. The pathogenesis of AHS is likely to represent the interplay between different factors, mainly immunological and genetic, and with the drug and accumulation of its metabolite (oxypurinol).