Impact of GGCX, STX1B and FPGS Polymorphisms on Warfarin Dose Requirements in European-Americans and Egyptians
| Author | Hamadeh, IS |
| Author | Shahin, MH |
| Author | Lima, SM |
| Author | Oliveira, F |
| Author | Wilson, L |
| Author | Khalifa, SI |
| Author | Langaee, TY |
| Author | Cooper-DeHoff, RM |
| Author | Cavallari, LH |
| Author | Johnson, JA |
| Available date | 2021-05-20T04:35:57Z |
| Publication Date | 2016 |
| Publication Name | Clinical and Translational Science |
| Resource | Scopus |
| ISSN | 17528054 |
| Abstract | 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. |
| Sponsor | This work was supported in part by National Institutes of Health grant GM074492 |
| Language | en |
| Publisher | Blackwell Publishing Ltd |
| Subject | adenine guanine protein STX1B protein VKORC1 tetrahydrofolate synthase unclassified drug vitamin K dependent carboxylase vitamin K epoxide reductase warfarin glutamyl carboxylase ligase microsatellite DNA peptide synthase STX1B protein, human syntaxin 1 tetrahydrofolate synthase warfarin adult aged Article cerebrovascular accident cohort analysis controlled study dose response drug dose reduction Egyptian European American gene linkage disequilibrium genetic association genotype human maintenance drug dose major clinical study priority journal single nucleotide polymorphism venous thromboembolism Caucasian Egypt female genetics male middle aged regression analysis single nucleotide polymorphism Adult Aged Carbon-Carbon Ligases Cohort Studies Dose-Response Relationship, Drug Egypt European Continental Ancestry Group Female Humans Linkage Disequilibrium Male Microsatellite Repeats Middle Aged Peptide Synthases Polymorphism, Single Nucleotide Regression Analysis Syntaxin 1 Warfarin |
| Type | Article |
| Pagination | 36-42 |
| Issue Number | 1 |
| Volume Number | 9 |
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