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首页> 外文期刊>Pharmacogenomics >Combined CYP2C9, VKORC1 and CYP4F2 frequencies among racial and ethnic groups.
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Combined CYP2C9, VKORC1 and CYP4F2 frequencies among racial and ethnic groups.

机译：种族和族裔群体中合并的CYP2C9，VKORC1和CYP4F2频率。

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AIMS: CYP4F2*3 (p.V433M) has been associated with higher warfarin dose requirements; however, its frequency, like other CYP2C9 and VKORC1 variants, has not been systematically assessed in major racial/ethnic populations. Thus, we determined the individual and combined frequencies of important CYP2C9, VKORC1 and CYP4F2 variants in several racial/ethnic groups. MATERIALS & METHODS: Healthy African-American, Asian, Caucasian, Hispanic and Ashkenazi Jewish (AJ) blood donors were genotyped for CYP2C9 (*2, *3, *4, *5, *6, *8, *11 and *13), VKORC1 (g.-1639G>A) and CYP4F2 (*3 [p.V433M] and rs2189784). RESULTS: The combined frequencies of variant CYP2C9 alleles were 0.133, 0.078, 0.212, 0.178 and 0.212 among African-American, Asian, Caucasian, Hispanic and AJ individuals, respectively. CYP4F2*3 frequencies were prevalent (0.233-0.342) among Asian, Caucasian, Hispanic and AJ individuals, while significantly less frequent among African-Americans (0.117; p < 0.0001). In addition, CYP4F2*3 was in linkage disequilibrium with rs2189784, an allele recently associated with time-to-therapeutic international normalized ratio, among all studied populations. Importantly, 87-95% of Asian, Caucasian, Hispanic and AJ individuals had a variant CYP2C9, VKORC1 and/or CYP4F2*3 allele, compared with only 53% of African-Americans (p < 0.0001). CONCLUSIONS: Compared with other racial/ethnic populations studied, only approximately one in 80 African-Americans were CYP4F2*3 homozygous, indicating that this population would benefit less from dosing algorithms that include this variant. In addition, the unique allele frequency profiles identified among the different populations partly explain why genotype-guided warfarin dosing algorithms perform less well for African-Americans and suggest that other unidentified genetic and/or nongenetic factors that influence warfarin dosage may exist in this population.
机译：目的：CYP4F2 * 3（p.V433M）与更高的华法林剂量要求有关;但是，它的频率与其他CYP2C9和VKORC1变体一样，尚未在主要种族/族裔人群中进行系统评估。因此，我们确定了几个种族/族裔群体中重要的CYP2C9，VKORC1和CYP4F2变异的个体频率和组合频率。材料与方法：对健康的非洲裔美国人，亚洲人，白种人，西班牙裔和阿什肯纳兹犹太人（AJ）的供血者进行CYP2C9基因分型（* 2，* 3，* 4，* 5，* 6，* 8，* 11和* 13） ），VKORC1（g.-1639G> A）和CYP4F2（* 3 [p.V433M]和rs2189784）。结果：在非洲裔美国人，亚裔，白种人，西班牙裔和AJ个体中，CYP2C9变异等位基因的组合频率分别为0.133、0.078、0.212、0.178和0.212。 CYP4F2 * 3频率在亚洲，白种人，西班牙裔和AJ患者中普遍存在（0.233-0.342），而在非裔美国人中则较不常见（0.117; p <0.0001）。此外，在所有研究人群中，CYP4F2 * 3与rs2189784存在连锁不平衡，rs2189784是最近与治疗时间国际标准化比率相关的等位基因。重要的是，在亚洲，白种人，西班牙裔和AJ人中，有87-95％的人具有CYP2C9，VKORC1和/或CYP4F2 * 3等位基因变异，而非裔美国人只有53％（p <0.0001）。结论：与其他种族/族裔人群相比，只有约八十分之一的非洲裔美国人是CYP4F2 * 3纯合子，表明该人群将从包括该变异体的给药算法中获益较少。此外，在不同人群中鉴定出的独特等位基因频率谱部分解释了为什么基因型指导的华法林剂量算法对非裔美国人的效果不佳，并暗示了影响华法林剂量的其他不确定的遗传和/或非遗传因素。

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