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University of Illinois – Chicago

1. Drozda, Katarzyna. Warfarin Pharmacogenomic Implementation: Implications for Minorities and Opportunities for Education.

Degree: 2014, University of Illinois – Chicago

Recent clinical trial results cast doubt on the utility of genotype-guided warfarin dosing, specifically showing worse dosing with a pharmacogenetic versus clinical dosing algorithm in African Americans. However, trials did not include many genotypes important in African Americans. We aimed to determine if omission of the CYP2C9*5, *6, *8, *11 and rs12777823G>A genotypes affects performance of pharmacogenetic dosing algorithms in African Americans. In a cohort of 274 warfarin-treated African Americans, we examined the association between CYP2C9*5, *6, *8, *11 and rs12777823G>A genotypes and warfarin dose prediction error with pharmacogenetic algorithms used in clinical trials. The warfarindosing.org algorithm over-estimated doses by a median (IQR) of 1.2 (0.02 to 2.6) mg/day in rs12777823 heterozygotes (p<0.001 for predicted versus observed doses), by 2.0 (0.6 to 2.8) mg/day with the rs12777823 A homozygotes (p=0.004), and by 2.2 (0.5 to 2.9) mg/day in carriers of a CYP2C9 variant (p<0.001). The International Warfarin Pharmacogenetics Consortium (IWPC) algorithm under-dosed warfarin by 0.8 (-2.3 to 0.4) mg/day for patients with the rs12777823 GG genotype (p<0.001) and over-dosed warfarin by 0.7 (-0.4 to 1.9) mg/day in carriers of a variant CYP2C9 allele (p=0.04). Modifying the warfarindosing.org algorithm to adjust for variants important in African Americans led to better dose prediction than either the original warfarindosing.org (p<0.01) or IWPC (p<0.01) algorithms. These data suggest that, when providing genotype-guided warfarin dosing, it is important to account for variants prevalent in African Americans to avoid significant dosing error in this population. Advisors/Committee Members: Zwanziger, Jack (advisor), Bishop, Jeffrey R. (committee member), Cavallari, Larisa H. (committee member), Nutescu, Edith A. (committee member), Schumock, Glen T. (committee member).

Subjects/Keywords: Pharmacogenomics; warfarin; genotype; CYP2C9; rs12777823

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Drozda, K. (2014). Warfarin Pharmacogenomic Implementation: Implications for Minorities and Opportunities for Education. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/19063

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Drozda, Katarzyna. “Warfarin Pharmacogenomic Implementation: Implications for Minorities and Opportunities for Education.” 2014. Thesis, University of Illinois – Chicago. Accessed March 05, 2021. http://hdl.handle.net/10027/19063.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Drozda, Katarzyna. “Warfarin Pharmacogenomic Implementation: Implications for Minorities and Opportunities for Education.” 2014. Web. 05 Mar 2021.

Vancouver:

Drozda K. Warfarin Pharmacogenomic Implementation: Implications for Minorities and Opportunities for Education. [Internet] [Thesis]. University of Illinois – Chicago; 2014. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/10027/19063.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Drozda K. Warfarin Pharmacogenomic Implementation: Implications for Minorities and Opportunities for Education. [Thesis]. University of Illinois – Chicago; 2014. Available from: http://hdl.handle.net/10027/19063

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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