Open AccessImpact of GGCX, STX1B and FPGS Polymorphisms on Warfarin Dose Requirements in European‐Americans and Egyptians
Author(s) -
Hamadeh IS,
Shahin MH,
Lima SM,
Oliveira F,
Wilson L,
Khalifa SI,
Langaee TY,
CooperDeHoff RM,
Cavallari LH,
Johnson JA
Publication year - 2016
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.12385
Subject(s) - vkorc1 , warfarin , cyp2c9 , vitamin k epoxide reductase , medicine , linkage disequilibrium , population , pharmacogenetics , oncology , genotype , pharmacology , biology , genetics , haplotype , cytochrome p450 , atrial fibrillation , gene , environmental health , metabolism
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.