Liu X, Sun J, Yu H, Chen H, Wang J, Zou H, Lu D, Xu J, Zheng S L
State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
Fudan Center for Genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai, China.
Pharmacogenomics J. 2015 Oct;15(5):467-72. doi: 10.1038/tpj.2015.7. Epub 2015 Mar 10.
Multiple HLA-B alleles (haplotypes) are associated with drug-induced adverse responses and disease risks but are difficult to be directly genotyped. The goal of this study is to identify single nucleotide polymorphisms (SNPs) that are able to tag HLA-B alleles in the Chinese Han population. Twelve HLA-B alleles that are associated with drug adverse responses and disease risks were identified. They were sequenced initially in 880 Chinese Han subjects where high-density SNPs within the HLA-B gene were available. Performances of these SNPs to tag the HLA-B alleles were assessed primarily by sensitivity and specificity. Two HLA-B alleles can be reliably tagged by SNPs at 100% sensitivity and >95% specificity. For example, HLA-B15:02 can be tagged by the 'C' allele of rs10484555, and HLA-B58:01 can be tagged by the 'T' allele of rs9262570. These results were confirmed in 500 additional Chinese Han subjects. If confirmed in independent studies, these tag SNPs could be used as a reliable, simple and cost-effective alternative for genotyping a subset of HLA-B alleles.
多种人类白细胞抗原B（HLA - B）等位基因（单倍型）与药物引起的不良反应及疾病风险相关，但难以直接进行基因分型。本研究的目的是在中国汉族人群中鉴定能够标记HLA - B等位基因的单核苷酸多态性（SNP）。已鉴定出12种与药物不良反应和疾病风险相关的HLA - B等位基因。最初在880名中国汉族受试者中对它们进行测序，这些受试者的HLA - B基因内有高密度SNP。这些SNP标记HLA - B等位基因的性能主要通过敏感性和特异性进行评估。两个HLA - B等位基因能够被SNP以100%的敏感性和>95%的特异性可靠地标记。例如，HLA - B15:02可被rs10484555的“C”等位基因标记，HLA - B58:01可被rs9262570的“T”等位基因标记。这些结果在另外500名中国汉族受试者中得到了证实。如果在独立研究中得到证实，这些标签SNP可作为一种可靠、简单且经济高效的替代方法，用于对一部分HLA - B等位基因进行基因分型。
