Abstract
The goal of this research was to investigate the linkage disequilibrium between rs9263726 and HLA-B*58:01 in different Chinese ethnic groups (Han, Tibet, and Hui) and to study the feasibility of rs9263726 replacing HLA-B*58:01 as an efficient indicator of potential allopurinol hypersensitivity syndrome. In this study, rs9263726 and HLA-B*58:01 were detected in all samples. For samples of individuals whose rs9263726 genotypes were not consistent with HLA-B*58:01, we did high-resolution typing of HLA-B gene to further confirm the correlation of rs9263726 genotype and special HLA-B alleles. We confirmed that the linkage disequilibrium between rs9263726 and HLA-B*58:01 was more significant in the Han ethnic group (r2=0.886, D’=1.0) than in the Tibet and Hui ethnic groups (for Tibetan, r2=0.606, D’=0.866; for Hui, r2=0.622, D’=0.924). For Han Chinese, samples with the GG genotype of rs9263726 did not carry HLA-B*58:01, while AA genotype samples were homozygous carriers of HLA-B*58:01. However, GA genotype samples of rs9263726 required a more sophisticated HLA-B genotyping assay before it was possible to identify whether they were HLA-B*58:01 carriers or not. For Tibetan and Hui, the linkage disequilibrium between rs9263726 and HLA-B*58:01 was not significant. Therefore, rs9263726 cannot replace HLA-B*58:01 in these two groups.
Highlights
Allopurinol is recommended as the first-line pharmacologic urate-lowering therapy in gout
HLA-B*58:01 has been recommended as marker of the severe allopurinol hypersensitivity syndrome in some subpopulations with high prevalence of the HLA-B*58:01 allele, including Chinese, European, Italian, Korean, and Thai (Pavlos et al, 2012)
Tohkin et al (2013) reported that rs9263726 was in absolute linkage disequilibrium (LD) with HLA-B*58:01 in a Japanese population and could be used as a surrogate marker of HLA-B*58:01 to predict patients with high-risk of severe allopurinol hypersensitivity syndrome
Summary
Allopurinol is recommended as the first-line pharmacologic urate-lowering therapy in gout. HLA-B*58:01 has been recommended as marker of the severe allopurinol hypersensitivity syndrome in some subpopulations with high prevalence of the HLA-B*58:01 allele, including Chinese, European, Italian, Korean, and Thai (Pavlos et al, 2012). Unlike the results for this Japanese population, a recent study showed a lack of LD between the rs9263726 A allele and HLA-B*58:01 in Australians (Vidal et al, 2016). This observation suggests that rs9263726 frequencies may differ across different ethnic groups
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