Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study
説明
<jats:title>Abstract</jats:title><jats:p>Graves’ disease is the leading cause of hyperthyroidism affecting 1.0–1.6% of the population. Antithyroid drugs are the treatment cornerstone, but may cause life-threatening agranulocytosis. Here we conduct a two-stage association study on two separate subject sets (in total 42 agranulocytosis cases and 1,208 Graves’ disease controls), using direct human leukocyte antigen genotyping and SNP-based genome-wide association study. We demonstrate <jats:italic>HLA-B*38:02</jats:italic> (Armitage trend <jats:italic>P</jats:italic><jats:sub>combined</jats:sub>=6.75 × 10<jats:sup>−32</jats:sup>) and <jats:italic>HLA-DRB1*08:03</jats:italic> (<jats:italic>P</jats:italic><jats:sub>combined</jats:sub>=1.83 × 10<jats:sup>−9</jats:sup>) as independent susceptibility loci. The genome-wide association study identifies the same signals. Estimated odds ratios for these two loci comparing effective allele carriers to non-carriers are 21.48 (95% confidence interval=11.13–41.48) and 6.13 (95% confidence interval=3.28–11.46), respectively. Carrying both <jats:italic>HLA-B*38:02</jats:italic> and <jats:italic>HLA-DRB1*08:03</jats:italic> increases odds ratio to 48.41 (<jats:italic>P</jats:italic><jats:sub>combined</jats:sub>=3.32 × 10<jats:sup>−21</jats:sup>, 95% confidence interval=21.66–108.22). Our results could be useful for antithyroid-induced agranulocytosis and potentially for agranulocytosis caused by other chemicals.</jats:p>
収録刊行物
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- Nature Communications
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Nature Communications 6 (1), 7633-, 2015-07-07
Springer Science and Business Media LLC