Pyrosequencing Method for Genotyping Cytochrome P450 CYP2C8 and CYP2C9 Enzymes

Hruska, Matthew; Frye, Reginald F.; Langaee, Taimour

doi:10.1373/clinchem.2004.040071

Cited by 30 publications

(23 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patients were genotyped for rs1799853, rs1057910, rs28371686, rs7900194, rs28371685, rs9923231, rs61162043, rs7089580, and rs12777823 using previously published methods. 14, 17, 18 A panel of 105 ancestry informative markers (AIMs) was genotyped for each patient to determine WAA. 19 Genotyping of AIMs was performed with the MassArray 7K HT genetic analysis system (Sequenom, Inc.) as previously described.…”

Section: Methodsmentioning

confidence: 99%

Ethnicity-specific pharmacogenetics: the case of warfarin in African Americans

et al. 2013

View full text Add to dashboard Cite

Using a derivation cohort (N=349), we developed the first warfarin dosing algorithm that includes recently discovered polymorphisms in VKORC1 and CYP2C9 associated with warfarin dose requirement in African Americans (AAs). We tested our novel algorithm in an independent cohort of 129 AAs and compared the dose prediction to the International Warfarin Pharmacogenetics Consortium (IWPC) dosing algorithms. Our algorithm explains more of the phenotypic variation (R2 = 0.27) than the IWPC pharmacogenomics (R2 = 0.15) or clinical (R2 = 0.16) algorithms. Among high dose patients, our algorithm predicted a higher proportion of patients within 20% of stable warfarin dose (45% vs. 29% and 2% in the IWPC pharmacogenomics and clinical algorithms respectively). In contrast to our novel algorithm, a significant inverse correlation between predicted dose and percent West African ancestry (WAA) was observed for the IWPC pharmacogenomics algorithm among patients requiring ≥60 mg/week (β = −2.04, p=0.02).

show abstract

Section: Methodsmentioning

confidence: 99%

Ethnicity-specific pharmacogenetics: the case of warfarin in African Americans

et al. 2013

View full text Add to dashboard Cite

show abstract

“…The CYP2C9 Arg144Cys polymorphism in exon 3 and the Ile359Leu and Asp360Glu polymorphisms in exon 7 were determined by polymerase chain reaction (PCR) and pyrosequencing, as previously described, to differentiate the *2 (144Cys), *3 (359Leu), and *5 (360Glu) alleles [14]. The VKORC1 G3673A (-1639G [ A) polymorphism was determined using previously described PCR and pyrosequencing techniques [15].…”

Section: Genotypingmentioning

confidence: 99%

Predictors of unstable anticoagulation in African Americans

Cavallari

Aston

Momary

et al. 2008

J Thromb Thrombolysis

View full text Add to dashboard Cite

We conclude that poor warfarin adherence and gastrointestinal illness are major contributors to unstable anticoagulation in African Americans. Our data suggest that, similar to Caucasians, improving warfarin adherence rates may be an important mean to improve anticoagulation control in African Americans. In addition, close monitoring during acute illness may be particularly important in this population.

show abstract

“…12, 13 For rs7089580, patients were genotyped through direct sequencing by PCR amplification of 1Kb overlapping fragments using a previously published method and primers. 5 In addition, a panel of 105 ancestry informative markers (AIMs) was also genotyped for all patients to determine West African ancestry.…”

Section: Methodsmentioning

confidence: 99%

Novel single nucleotide polymorphism in CYP2C9 is associated with changes in warfarin clearance and CYP2C9 expression levels in African Americans

Hernandez

Aquino‐Michaels

Drozda

et al. 2015

Translational Research

View full text Add to dashboard Cite

Warfarin is a widely used anticoagulant whose active S-enantiomer is primarily metabolized by the CYP2C9 enzyme. The CYP2C9*2 and CYP2C9*3 alleles are associated with lower warfarin dose requirement and decreased enzyme activity. In contrast, we previously identified a novel SNP (rs7089580 A>T) in CYP2C9 that is associated with higher warfarin dose requirement in African Americans. In this study, we examine the effect of rs7089580 on warfarin pharmacokinetics and CYP2C9 expression in 63 African American patients and 32 African American liver tissues, respectively. We found oral clearance of S-warfarin to be higher among carriers of the minor rs7089580 allele (T) compared to wild type homozygotes (3.73±1.46 ml/min vs. 2.95±1.39 ml/min, p=0.04). CYP2C9 mRNA expression in liver tissue was also higher among A/T and T/T genotypes compared to A/A (p<0.02). Our findings indicate that rs7089580 is associated with higher S-warfarin clearance and CYP2C9 expression and may help explain the higher dose requirement of warfarin in African Americans. Furthermore, rs7089580 is in complete linkage disequilibrium with the promoter SNP rs12251841 in African Americans which may provide a biologically plausible explanation for the observed effect on CYP2C9 expression levels. Given the many clinically relevant substrates of CYP2C9, identifying polymorphisms that affect expression levels and metabolism across ethnicities is essential for individualization of doses with a narrow therapeutic index.

show abstract

Pyrosequencing Method for Genotyping Cytochrome P450 CYP2C8 and CYP2C9 Enzymes

Cited by 30 publications

References 17 publications

Ethnicity-specific pharmacogenetics: the case of warfarin in African Americans

Ethnicity-specific pharmacogenetics: the case of warfarin in African Americans

Predictors of unstable anticoagulation in African Americans

Novel single nucleotide polymorphism in CYP2C9 is associated with changes in warfarin clearance and CYP2C9 expression levels in African Americans

Contact Info

Product

Resources

About