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PMID: 19802360 Published · ppublish English Journal Article

Influence of CYP2C9 Genotype on warfarin dose among African American and European Americans.

Personalized medicine ·Vol. 4 ·No. 2 ·2007-05-01 ·Pages 157-169

Limdi N, Goldstein J, Blaisdell J, Beasley T, Rivers C, Acton R

Abstract

BACKGROUND: Cytochrome P4502C9 (CYP2C9) plays a vital role in drug metabolism. There has been an increased effort to identify polymorphisms within the gene and determine their clinical consequences. However, most of these efforts have focused on populations of European descent. Herein we report the influence of CYP2C9 genotype on warfarin dose among European American and African American patients. We also identify two new mutations; one in the coding region and one in the non-coding region of the CYP2C9 gene. METHODS: Patients (≥20 years of age) are enrolled after obtaining medical, lifestyle and concomitant medication history. Changes in International Normalized Ratio (INR), warfarin dose, co-medications, diet, physical activity and the occurrence of complications are documented. CYP2C9 genotype was determined using PCR-RFLP and pyrosequencing. Differences in genotype frequencies and HWE assumptions were assessed using χ(2) statistics and exact tests. The genotype dose association was evaluated using multivariable linear regression. RESULTS: This report includes 490 patients (mean age 60.6 ± 15.6, 51.3% men). African American patients comprise 48.9% of the cohort with mean follow-up of 13.5 (±10.6) months. Both the CYP2C9 *2 and *3 allele were more frequent in European Americans (11.24%, 5.1%) compared to African Americans (1.1% and 1.8%). CYP2C9 *5 (0.9%), *6 (0.4%), and *11 (1.1%) variants were only observed in African Americans. The variant genotype is more frequent among European Americans compared to African Americans (29.8% vs. 9.73%, p<0.0001). Warfarin dose was significantly related to CYP2C9 genotype (p<0.0001) both in univariate and multivariate analyses. Multivariable race-specific analyses highlight the contribution of CYP2C9 genotype among European American but not among African American patients. CONCLUSION: The variant CYP2C9 genotype is more frequent among European Americans compared to African Americans. Among African Americans the variant genotype frequency is higher than previously reported. CYP2C9 genotype predicts warfarin dose in European Americans, but not in African Americans.

Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Limdi Na
Departments of Neurology, University of Alabama at Birmingham, AL.
Goldstein Ja
Blaisdell Ja
Beasley Tm
Rivers Ca
Acton Rt
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Article Info
Journal
Personalized medicine
Abbr.
Per Med
ISSN
1741-0541
DOI
10.2217/17410541.4.2.157
Published
2007-05-01
Pages
157-169
Language
English
Region
England
NLM ID
101238549
PMCID
PMC2756088
Grants
NINDS NIH HHS · K23 NS045598 · United States
NINDS NIH HHS · K23 NS045598-03 · United States
External Links
PubMed source DOI: 10.2217/17410541.4.2.157 PMC Full Text View journal details
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