一项基于药物遗传学的中国北方患者华法林维持剂量算法。
A pharmacogenetics-based warfarin maintenance dosing algorithm from Northern Chinese patients.
作者信息
Chen Jinxing, Shao Liying, Gong Ling, Luo Fang, Wang Jin'e, Shi Yi, Tan Yu, Chen Qianlong, Zhang Yu, Hui Rutai, Wang Yibo
机构信息
State Key Laboratory of Cardiovascular Disease, Sino-German Laboratory for Molecular Medicine, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
State Key Laboratory of Cardiovascular Disease, Sino-German Laboratory for Molecular Medicine, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
出版信息
PLoS One. 2014 Aug 15;9(8):e105250. doi: 10.1371/journal.pone.0105250. eCollection 2014.
Inconsistent associations with warfarin dose were observed in genetic variants except VKORC1 haplotype and CYP2C93 in Chinese people, and few studies on warfarin dose algorithm was performed in a large Chinese Han population lived in Northern China. Of 787 consenting patients with heart-valve replacements who were receiving long-term warfarin maintenance therapy, 20 related Single nucleotide polymorphisms were genotyped. Only VKORC1 and CYP2C9 SNPs were observed to be significantly associated with warfarin dose. In the derivation cohort (n = 551), warfarin dose variability was influenced, in decreasing order, by VKORC1 rs7294 (27.3%), CYP2C93(7.0%), body surface area(4.2%), age(2.7%), target INR(1.4%), CYP4F2 rs2108622 (0.7%), amiodarone use(0.6%), diabetes mellitus(0.6%), and digoxin use(0.5%), which account for 45.1% of the warfarin dose variability. In the validation cohort (n = 236), the actual maintenance dose was significantly correlated with predicted dose (r = 0.609, P<0.001). Our algorithm could improve the personalized management of warfarin use in Northern Chinese patients.
在中国人群中，除了VKORC1单倍型和CYP2C93外，在基因变异中观察到与华法林剂量的关联不一致，并且针对居住在中国北方的大型汉族人群进行的华法林剂量算法研究很少。在787名接受长期华法林维持治疗的心脏瓣膜置换术同意患者中，对20个相关单核苷酸多态性进行了基因分型。仅观察到VKORC1和CYP2C9单核苷酸多态性与华法林剂量显著相关。在推导队列（n = 551）中，华法林剂量变异性受以下因素影响，影响程度从高到低依次为：VKORC1 rs7294（27.3%）、CYP2C93（7.0%）、体表面积（4.2%）、年龄（2.7%）、目标国际标准化比值（1.4%）、CYP4F2 rs2108622（0.7%）、使用胺碘酮（0.6%）、糖尿病（0.6%）和使用地高辛（0.5%），这些因素占华法林剂量变异性的45.1%。在验证队列（n = 236）中，实际维持剂量与预测剂量显著相关（r = 0.609，P<0.001）。我们的算法可以改善中国北方患者华法林使用的个性化管理。
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