Effect of NQO1 and CYP4F2 genotypes on warfarin dose requirements in Hispanic-Americans and African-Americans.
Effect of NQO1 and CYP4F2 genotypes on warfarin dose requirements in Hispanic-Americans and African-Americans.
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DOI：
10.2217/pgs.12.164
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发表时间：
2012-12
期刊：
影响因子：
2.1
通讯作者：
Cavallari LH
中科院分区：
文献类型：
--
作者：
Bress A;Patel SR;Perera MA;Campbell RT;Kittles RA;Cavallari LH
本研究的目的是在考虑已知的临床和遗传预测因子后，确定NQO 1和CYP 4F 2基因型对两个种族组华法林剂量需求的额外贡献。在260名非洲裔美国人和53名西班牙裔美国人的队列中评估了以下内容：临床数据; NQO 1 p.P187S（*1/*2）; CYP 2C 9 *2、*3、*5、*6、*8和 *11; CYP 4F 2 p.V433M;和VKORC 1 c.- 1639 G>A基因型。西班牙裔美国人的CYP 4F 2 433 M（0.23 vs. 0.06; p < 0.05）和NQO 1 *2（0.27 vs. 0.18; p < 0.05）等位基因频率均高于非洲裔美国人。西班牙裔美国人队列的多元回归分析显示，每个CYP 4F 2 433 M等位基因与华法林维持剂量增加22%相关（p = 0.019）。在调整相关遗传因素（CYP 2C 9、CYP 4F 2和VKORC 1）和临床因素后，NQO 1 *2等位基因的携带与华法林维持剂量增加34%相关（p = 0.004）。在该人群中，纳入CYP 4F 2和NQO 1 *2基因型将模型解释的剂量变异性从0.58改善至0.68（p = 0.001），相对改善17%。相比之下，在调整已知的遗传和临床预测因子后，CYP 4F 2或NQO 1 *2基因型与非洲裔美国人的华法林治疗剂量之间没有关联。在我们的市中心西班牙裔美国人队列中，CYP 4F 2和NQO 1 *2基因型显著影响华法林剂量需求。如果我们的研究结果得到证实，他们将表明，在华法林剂量预测算法中纳入CYP 4F 2和NQO 1 *2基因型可能会提高此类算法在西班牙裔美国人中的预测能力。
The objective of this study was to determine the additional contribution of NQO1 and CYP4F2 genotypes to warfarin dose requirements across two racial groups after accounting for known clinical and genetic predictors. The following were assessed in a cohort of 260 African–Americans and 53 Hispanic–Americans: clinical data; NQO1 p.P187S (*1/*2); CYP2C9*2, *3, *5, *6, *8 and *11; CYP4F2 p.V433M; and VKORC1 c.-1639G>A genotypes. Both the CYP4F2 433M (0.23 vs 0.06; p < 0.05) and NQO1*2 (0.27 vs. 0.18; p < 0.05) allele frequencies were higher in Hispanic–Americans compared with African–Americans. Multiple regression analysis in the Hispanic–American cohort revealed that each CYP4F2 433M allele was associated with a 22% increase in warfarin maintenance dose (p = 0.019). Possession of the NQO1*2 allele was associated with a 34% increase in warfarin maintenance dose (p = 0.004), while adjusting for associated genetic (CYP2C9, CYP4F2 and VKORC1) and clinical factors. In this population, the inclusion of CYP4F2 and NQO1*2 genotypes improved the dose variability explained by the model from 0.58 to 0.68 (p = 0.001), a 17% relative improvement. By contrast, there was no association between CYP4F2 or NQO1*2 genotype and therapeutic warfarin dose in African–Americans after adjusting for known genetic and clinical predictors. In our cohort of inner-city Hispanic–Americans, the CYP4F2 and NQO1*2 genotypes significantly contributed to warfarin dose requirements. If our findings are confirmed, they would suggest that inclusion of the CYP4F2 and NQO1*2 genotypes in warfarin dose prediction algorithms may improve the predictive ability of such algorithms in Hispanic–Americans.
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影响因子：
4.1
作者：
Andrisin, TE;Humma, LM;Johnson, JA
通讯作者：
Johnson, JA
影响因子：
2.1
作者：
Borgiani, P.;Ciccacci, C.;Novelli, G.
通讯作者：
Novelli, G.
影响因子：
2.3
作者：
Cavallari, Larisa H.;Momary, Kathryn M.;Viana, Marlos A. G.
通讯作者：
Viana, Marlos A. G.
影响因子：
158.5
作者：
Budnitz, Daniel S.;Lovegrove, Maribeth C.;Richards, Chesley L.
通讯作者：
Richards, Chesley L.
影响因子：
6.7
作者：
Geisen, C;Watzka, M;Oldenburg, J
通讯作者：
Oldenburg, J