Factors influencing warfarin dose requirements in African-Americans
Factors influencing warfarin dose requirements in African-Americans
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DOI：
10.2217/14622416.8.11.1535
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发表时间：
2007-11-01
期刊：
影响因子：
2.1
通讯作者：
Cavallari, Larisa H.
中科院分区：
文献类型：
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作者：
Momary, Kathryn M.;Shapiro, Nancy L.;Cavallari, Larisa H.
引言：非裔美国人在评估华法林反应的贡献因素的研究中代表性不足。我们的主要目的是确定细胞色素P450 (CYP) 2C9、烟酰胺腺嘌呤二核苷酸磷酸、还原醌氧化还原酶（NQO1）和维生素K环氧化物还原酶复合物亚基1 （VKORC1）基因是否与非裔美国人的华法林剂量需求有关。患者和方法：评估以下因素：人口统计学；临床数据;CYP2C9基因Arg144Cys（*2）、Ile358Leu（*3）、Asp360Glu (*5)；NQO1 Pro187Ser (* 1 /*2)；对115名服用稳定剂量华法林的非洲裔美国人的VKORC1 G6853C基因型进行了分析。结果：CYP2C9 *2、*3、*5等位基因频率均为0.05；NQO1 *2 0.20；VKORC1 6853C为0.25。与*1/*1基因型患者相比，CYP2C9*2、*3或*5等位基因与华法林剂量降低38%相关（30:1:13 vs 48 +/- 18 mg/周；p = 0.003）。在整个人群或CYP2C9*1等位基因纯合子中，NQO1 *1/*2和VKORC1 G6853C基因型均与华法林剂量需求无关。多元回归分析显示，CYP2C9基因型（p = 0.015）、年龄（p < 0.001）和体表面积（p < 0.001）与华法林剂量需求共同相关，它们共同解释了33%的非裔美国人华法林剂量需求差异。讨论：我们的数据表明CYP2C9基因型、年龄和体型是非裔美国人华法林剂量需求的重要决定因素。我们的数据进一步表明，单独的VKORC1 G6853C多态性可能不能用于预测该种族人群的华法林剂量需求。
Introduction: African-Americans are under-re presented in studies assessing contributors to warfarin response. Our primary objective was to determine whether the genes for cytochrome P450 (CYP) 2C9, nicotinamide adenine dinucleotide phosphate, reduced, quinone oxidoreductase (NQO1) and vitamin K epoxide reductase complex subunit 1 (VKORC1) are associated with warfarin dose requirements in African-Americans. Patients and methods: The following factors were assessed: demographics; clinical data; the CYP2C9 Arg144Cys (*2), Ile358Leu (*3) and Asp360Glu (*5); NQO1 Pro187Ser (*l/*2); and VKORC1 G6853C genotypes were analyzed in 115 African-Americans on stable warfarin doses. Results: Allele frequencies were 0.05 for the CYP2C9 *2, *3 or *5 alleles; 0.20 for NQO1 *2; and 0.25 for VKORC1 6853C. Possession of a CYP2C9*2, *3 or *5 allele was associated with a 38% lower warfarin dose compared with the *1/*1 genotype (30 :1: 13 vs 48 +/- 18 mg/week; p = 0.003). Neither the NQO1 *1/*2 nor VKORC1 G6853C genotype was associated with warfarin dose requirements in the population as a whole or in CYP2C9*1 allele homozygotes. Multiple regression analysis revealed that CYP2C9 genotype (p = 0.015), age (p < 0.001) and body surface area (p < 0.001) were jointly associated with warfarin dose requirements, and together explained 33% of the variability in warfarin dose requirements among African-Americans. Discussion: Our data suggest that CYP2C9 genotype, age and body size are important determinants of warfarin dose requirements in African-Americans. Our data further suggest that the VKORC1 G6853C polymorphism alone may not be useful for predicting warfarin dose requirements in this racial group.