講演情報
[OE2-5]corePGseq: HLA遺伝子および非翻訳領域を含むPGx関連18遺伝子のターゲットシークエンシング法のためのパネル
○福永 航也1,2, 莚田 泰誠1 (1.理化学研究所 生命医科学研究センター ファーマコゲノミクス研究チーム, 2.国立医薬品食品衛生研究所 医薬安全科学部)
[Introduction] Pharmacogenetic testing for several pharmacogenes has been implemented to predict the risk of adverse drug reactions (ADRs) and drug responses. However, more practical sequencing method has been required to implement the pharmacogenomic biomarkers in clinical practices. Here, we developed corePGseq, a targeted next-generation sequencing panel for pharmacogenetic testing of 18 pharmacogenes, including four human leucocyte antigen (HLA) genes and the essential coding and non-coding regions in the pharmacogenes.
[Methods] Specific primers were designed to amplify crucial regions of 18 pharmacogenes, including HLA and cytochrome P450 (CYP) 2D6 genes. The concordance rate of genotypes in 78 Caucasian, 104 Chinese, 105 Japanese and 106 African individuals was evaluated compared with the genotypes identified by the conventional genotyping methods.
[Results] Concordance rates of HLA-A, HLA-B, HLA-DRB1 and HLA-DQA1 genotypes at 4-digit resolution in the 393 individuals derived from four populations were 99.5%, 99.7%, 98.3% and 100.0%, respectively. Especially, the HLA genotypes of Japanese individuals were completely the same between corePGseq panel and sequence-based HLA typing. The concordance rate of the CYP2D6 genotypes that includes copy number variations was 98.4% in comparison with those by whole genome sequencing. The genotypes of CYP2C9, CYP2C19, CYP3A5, DPYD, NAT2, SLCO1B1, TPMT, UGT1A1 and VKORC1 genes showed a 100% match.
[Discussion] We developed corePGseq, a high throughput and high accurate method to identify the genotypes of 18 pharmacogenes.
[Methods] Specific primers were designed to amplify crucial regions of 18 pharmacogenes, including HLA and cytochrome P450 (CYP) 2D6 genes. The concordance rate of genotypes in 78 Caucasian, 104 Chinese, 105 Japanese and 106 African individuals was evaluated compared with the genotypes identified by the conventional genotyping methods.
[Results] Concordance rates of HLA-A, HLA-B, HLA-DRB1 and HLA-DQA1 genotypes at 4-digit resolution in the 393 individuals derived from four populations were 99.5%, 99.7%, 98.3% and 100.0%, respectively. Especially, the HLA genotypes of Japanese individuals were completely the same between corePGseq panel and sequence-based HLA typing. The concordance rate of the CYP2D6 genotypes that includes copy number variations was 98.4% in comparison with those by whole genome sequencing. The genotypes of CYP2C9, CYP2C19, CYP3A5, DPYD, NAT2, SLCO1B1, TPMT, UGT1A1 and VKORC1 genes showed a 100% match.
[Discussion] We developed corePGseq, a high throughput and high accurate method to identify the genotypes of 18 pharmacogenes.