Schelleman H, Chen Z, Kealey C, Whitehead A S, Christie J, Price M, Brensinger C M, Newcomb C W, Thorn C F, Samaha F F, Kimmel S E
Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics & Epidemiology, University of Pennsylvania School of Medicine, and Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.
Clin Pharmacol Ther. 2007 May;81(5):742-7. doi: 10.1038/sj.clpt.6100144. Epub 2007 Feb 28.
The objective of this study was to determine whether two vitamin K epoxide reductase complex 1 (VKORC1) polymorphisms contribute to the variability in warfarin response, particularly in African Americans. The effect of the VKORC1 1173C/T and -1639G/A polymorphisms was examined in a prospective cohort study of 338 warfarin users. Subjects carrying an 1173T allele had a lower warfarin maintenance dose compared with subjects with the CC genotype in African Americans (-12.10 mg/week+/-4.93; P=0.02) and Caucasians (-14.41 mg/week+/-3.28; P<0.001). Before reaching maintenance dose, only Caucasians with the T allele had significantly increased risk of international normalized ratio >3 (odds ratio=3.10; 95% confidence interval: 1.73-5.55) compared with Caucasians with the CC genotype. Polymorphisms in the VKORC1 gene are associated with warfarin maintenance dose requirements among both African Americans and Caucasians. However, these polymorphisms may not be as useful in predicting over-anticoagulation among African Americans.
本研究的目的是确定维生素K环氧化物还原酶复合体1（VKORC1）的两种多态性是否会导致华法林反应的变异性，尤其是在非裔美国人中。在一项对338名华法林使用者的前瞻性队列研究中，检测了VKORC1 1173C/T和-1639G/A多态性的影响。在非裔美国人中，携带1173T等位基因的受试者与CC基因型受试者相比，华法林维持剂量较低（-12.10 mg/周±4.93；P=0.02）；在白种人中也是如此（-14.41 mg/周±3.28；P<0.001）。在达到维持剂量之前，与CC基因型的白种人相比，只有携带T等位基因的白种人国际标准化比值>3的风险显著增加（比值比=3.10；95%置信区间：1.73-5.55）。VKORC1基因的多态性与非裔美国人和白种人的华法林维持剂量需求相关。然而，这些多态性在预测非裔美国人的抗凝过度方面可能不太有用。
