背景:药物基因组学(PGx)研究了遗传变异对药物反应的影响。随着越来越多的临床遗传学实施联盟(CPIC)指南的发表,PGx正逐渐从单基因的反应性测试转向多基因的抢先性测试。但是PGx基因的特征,特别是国内的多样性,在中国不是很了解。
方法:我们回顾性收集了来自中国20个省的22,918名参与者的抢先PGx测试数据,分析了等位基因的频率,药物基因的基因型和表型,预测每个参与者的药物反应,并在不同省份之间进行了比较。
结论:在分析了31种药物的CPIC指南中的15种药物来源后,我们发现,99.97%的个体可能对至少一种药物有不典型的反应;参与者携带可操作的基因型,导致不典型的推荐剂量,中位数为8种药物.超过99%的参与者根据遗传因素建议减少华法林剂量。有20种药物的高风险比例从0.18%到58.25%,其中氯吡格雷的高危比例最高。此外,广东(RR=13.17,95CI:4.06~33.22,p<0.001)和广西(RR=23.44,95CI:8.83~52.85,p<0.001)的rasburicase高危比例明显高于各省。此外,我们观察到的20个省份的多样性表明,在中国不同地理区域的先发制人PGx检测可能需要更多地关注特定基因。这些结果强调了先发制人PGx检测的重要性,并为促进中国临床实施提供了必要的证据。
BACKGROUND: Pharmacogenomics (PGx) examines the influence of genetic variation on drug responses. With more and more Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines published, PGx is gradually shifting from the reactive testing of single gene toward the preemptive testing of multiple genes. But the profile of PGx genes, especially for the intra-country diversity, is not well understood in China.
METHODS: We retrospectively collected preemptive PGx testing data of 22,918 participants from 20 provinces of China, analyzed frequencies of alleles, genotypes and phenotypes of pharmacogenes, predicted drug responses for each participant, and performed comparisons between different provinces.
CONCLUSIONS: After analyzing 15 pharmacogenes from CPIC guidelines of 31 drugs, we found that 99.97% of individuals may have an atypical response to at least one drug; the participants carry actionable genotypes leading to atypical dosage recommendation for a median of eight drugs. Over 99% of the participants were recommended a decreased warfarin dose based on genetic factors. There were 20 drugs with high-risk ratios from 0.18% to 58.25%, in which clopidogrel showed the highest high-risk ratio. In addition, the high-risk ratio of rasburicase in GUANGDONG (risk ratio (RR) = 13.17, 95%CI:4.06-33.22, p < 0.001) and GUANGXI (RR = 23.44, 95%CI:8.83-52.85, p < 0.001) were significantly higher than that in all provinces. Furthermore, the diversity we observed among 20 provinces suggests that preemptive PGx testing in different geographical regions in China may need to pay more attention to specific genes. These results emphasize the importance of preemptive PGx testing and provide essential evidence for promoting clinical implementation in China.