GGCX、STX1B和FPGS基因多态性对欧美人和埃及人华法林剂量需求的影响
Impact of GGCX, STX1B and FPGS Polymorphisms on Warfarin Dose Requirements in European-Americans and Egyptians.
作者信息
Hamadeh I S, Shahin M H, Lima S M, Oliveira F, Wilson L, Khalifa S I, Langaee T Y, Cooper-DeHoff R M, Cavallari L H, Johnson J A
机构信息
Center for Pharmacogenomics, Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, Florida, USA.
Florida A&M University College of Pharmacy, Tallahassee, Florida, USA.
出版信息
Clin Transl Sci. 2016 Feb;9(1):36-42. doi: 10.1111/cts.12385. Epub 2016 Jan 19.
Genotype-based algorithms that include VKORC1 and CYP2C9 genotypes are less predictive of warfarin dose variability in Africans as opposed to Europeans. Polymorphisms in GGCX, FPGS, or STX1B are associated with warfarin dose requirements in African-Americans. We sought to determine if they influenced warfarin dose in European-Americans, and another African population, specifically Egyptians. We genotyped 529 adults (n = 325 European-Americans, 204 Egyptians) on a stable warfarin dose for GGCX rs12714145 and rs10654848, FPGS rs7856096, and STX1B rs4889606. Rs12714145, rs10654848, and rs7856096 were not associated with warfarin dose, whereas STX1B rs4889606 was a significant determinant in univariate analysis (P < 0.0001) in both cohorts. However, STX1B rs4889606 was in high linkage disequilibrium with VKORC1-1639 G>A, and was no longer significant after including VKORC1-1639 G>A in the regression model. Based on these data, the polymorphisms do not appear to influence, in a clinically important way, warfarin dose requirements in European-Americans and Egyptians.
与欧洲人相比，包含维生素K环氧化物还原酶复合体亚单位1（VKORC1）和细胞色素P450 2C9（CYP2C9）基因型的基于基因型的算法对非洲人华法林剂量变异性的预测性较低。γ-谷氨酰羧化酶（GGCX）、叶酸聚谷氨酸合成酶（FPGS）或 syntaxin 1B（STX1B）的多态性与非裔美国人的华法林剂量需求相关。我们试图确定它们是否会影响欧裔美国人和另一个非洲人群（具体为埃及人）的华法林剂量。我们对529名服用稳定华法林剂量的成年人（n = 325名欧裔美国人，204名埃及人）进行了GGCX rs12714145和rs10654848、FPGS rs7856096以及STX1B rs4889606的基因分型。Rs12714145、rs10654848和rs7856096与华法林剂量无关，而STX1B rs4889606在两个队列的单变量分析中均为显著决定因素（P < 0.0001）。然而，STX1B rs4889606与VKORC1 - 1639 G>A处于高度连锁不平衡状态，在回归模型中纳入VKORC1 - 1639 G>A后不再显著。基于这些数据，这些多态性似乎不会以临床上重要的方式影响欧裔美国人和埃及人的华法林剂量需求。
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