期刊
AMERICAN JOURNAL OF THERAPEUTICS
卷 28, 期 4, 页码 E461-E468出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MJT.0000000000000845
关键词
warfarin dose; genetic polymorphism; VKORC1
资金
- Korea Health Technology R&D Project through the Korea Clinical Trials Global Initiative - Ministry of Health Welfare [HI14C1731]
- National Research Foundation of Korea, Republic of Korea [2015R1D1A1A09057025]
- National Research Foundation of Korea [2015R1D1A1A09057025] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The study found that Korean patients require lower warfarin doses than Caucasians, potentially due to genetic polymorphism differences.
Background: Conventional anticoagulation with warfarin remains the cornerstone strategy for numerous preventive strategies. It is established that Asian patients require lower warfarin doses than Caucasians potentially attributing to the genetic polymorphism (GP) differences. Areas of Uncertainty: The impact of GP on optimal warfarin dose (OWD) in Koreans is unclear when compared with other ethnicities. It is also not well established whether GP linked to OWD in Korean patients to the similar extend as in Chinese, Japanese, and Caucasians. Data Sources: Single-center prospective observational study in Koreans, matched with historic cohorts of other ethnicities. Therapeutic Advances: Clinical characteristics, concomitant medications, OWD, international normalized ratio, and VKORC1, CYP2C9, and CYP4F2 GPs were assessed in consecutive Korean patients. The OWD was defined when patient's international normalized ratio was within target range for at least 3 consecutive times separated by 1 week. We included 133 (mean age 62.6 +/- 12.1 years, 49% males) warfarin-treated patients of Korean descend. The mean OWD was 3.30 +/- 1.34 (range: 1-9) mg/d. Homozygous wild-type patients required lower OWD (3.1 +/- 1.1 mg/d vs. 4.7 +/- 1.8 mg/d, P < 0.001) for VKORC1 and higher OWD for both CYP2C9 (3.4 +/- 1.3 mg/d vs. 2.3 +/- 1.1 mg/d, P = 0.002) and CYP4F2 (3.0 +/- 1.2 mg/d vs. 3.4 +/- 1.3 mg/d vs. 4.0 +/- 1.7 mg/d, P = 0.033) than those carrying heterozygote genes. Conclusions: Korean patients exhibit different VKORC1, CYP2C9, and CYP4F2 profiles impacting lower OWD in Eastern Asians than required in Caucasians. Universal international OWD guidelines may consider patient ethnicity as a confounder; however, this hypothesis needs further clarification.
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