Genetic Epidemiology of Pharmacogenetic Variations in
 CYP2C9
 ,
 CYP4F2
 and
 VKORC1
 Genes Associated with Warfarin Dosage in the Indian Population

Giri, Anil; Khan, Nazir M.; Grover, Sandeep; Kaur, Ishwinder; Basu, Analabha; Tandon, Nikhil; Scaria, Vinod; Indico,; Kukreti, Ritushree; Brahmachari, Samir K.; Bharadwaj, Dwaipayan

doi:10.2217/pgs.14.88

Cited by 34 publications

(33 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To avoid toxicity or treatment failure, population-based dose recommendations for drugs metabolized by CYP2C9, particularly warfarin is suggested (Giri et al, 2014;Wadelius, 2014). Most of these recommendations and dose algorithms are based on genotype.…”

Section: Introductionmentioning

confidence: 99%

“…However, the extent of correlation between CYP2C9 genotype and phenotype varies between populations mainly due to the contribution of sociodemographic, epigenetic, or environmental factors, such as diet. Numerous factors affecting CYP2C9 enzyme activity have been described, including genotype, gender, age, cigarette smoking, oral contraceptives, and food constituents (Bazan et al, 2014;Giri et al, 2014;Hidaka et al, 2008;Sandberg et al, 2004). These factors might be important to consider for dose modifications (Bazan et al, 2014;Lee et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differences inCYP2C9Genotype and Enzyme Activity Between Swedes and Koreans of Relevance for Personalized Medicine: Role of Ethnicity, Genotype, Smoking, Age, and Sex

Hatta

Lundblad

Ramsjö

et al. 2015

OMICS: A Journal of Integrative Biology

View full text Add to dashboard Cite

Global personalized medicine demands the characterization of person-to-person and between-population differences in drug pharmacokinetics and pharmacodynamics. CYP2C9 pharmacokinetic pathway is subject to modulation by both genetic and environmental factors. CYP2C9 genotype-based dose recommendations (e.g., for warfarin) is advocated. However, the overall contribution of genotype for variation in enzyme activity may differ between populations. We evaluated the importance of ethnicity, genotype, smoking, body weight, age, and sex for CYP2C9 enzyme activity. CYP2C9 genotype and phenotype was determined in 148 Swedes and 146 Koreans using losartan as a probe. CYP2C9 enzyme activity was assessed using urinary losartan/metabolite E-3174 ratio. The frequency of CYP2C9 defective variant alleles (*2 and *3) was significantly higher in Swedes (10.8% and 12.5%) than in Koreans (0% and 5.8%). In matched genotypes, CYP2C9 enzyme activity was significantly lower in Swedes compared to Koreans (p<0.0001). In a univariate analysis, age, weight, ethnicity, genotype, and smoking were significant predictors of CYP2C9 phenotype. A stepwise multivariate analysis indicated ethnicity, genotype, and smoking remained as significant predictors of CYP2C9 enzyme activity, accounting for 50% of the total variance. In both study populations, CYP2C9 genotype was a significant predictor of CYP2C9 enzyme activity, but its contribution in explaining the total variance was lower in Koreans (26.6%) than Swedes (40%). In conclusion, we report significantly lower CYP2C9 enzyme activity in Swedes compared to Koreans, partly but not exclusively due to CYP2C9 pharmacogenetic variations. Ethnicity and environment factors need to be considered together with genotype for population-specific dose optimization and global personalized medicine.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differences inCYP2C9Genotype and Enzyme Activity Between Swedes and Koreans of Relevance for Personalized Medicine: Role of Ethnicity, Genotype, Smoking, Age, and Sex

Hatta

Lundblad

Ramsjö

et al. 2015

OMICS: A Journal of Integrative Biology

View full text Add to dashboard Cite

show abstract

“…As the instability by VKORC1-1639G>A polymorphism is distinct by ancestral groups 24 . The allelic distribution of VKORC11639G>A showed a great degree of high prevalence across Sudanese patients different ethnical groups, being similar to the Indian populations different ethnicities, with VKORC1-1639G>A allele frequencies which were found to be as low as 6.5% and up to 70% 25 . But, our results are quite different from the Chinese population whose genetic data had accounted for 90% of homozygous mutant VKORC1/AA genotype and only 10% of VKORC1/GA heterozygous genotype profile 26 .…”

Section: Vkorc1-1639g>amentioning

confidence: 56%

Genetic and Non-Genetic Factors Association with Warfarin Long Term Therapy Stability in Sudan

Aldahab¹,

Elkhawad²

2016

AJPRHC

View full text Add to dashboard Cite

Anticoagulation with warfarin is characterized by a wide inter-individual variations in dose requirements and INR (International Normalised Ratio) stability, as there are evidences that warfarin response variability is associated with CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) and VKORC1 (Vitamin K epoxide reductase complex1) genetic polymorphisms. Carriers of CYP2C9*2 and VKORC11639G>A variant alleles are at greater risk of unstable anticoagulation therapy. Objectives: This retrospective case control study was directed to analyze the impact of genetic and non-genetic factors on warfarin therapy in Sudanese out-patients who were on long term warfarin therapy. Method: 118 Sudanese outpatients receiving warfarin treatment for at least six months, were interviewed for their non-genetic factors that included age, sex, indication for warfarin therapy, compliance, Vitamin K rich foods intake and concomitant drug therapy, in addition to their blood samples which were taken for DNA extraction and genotyping of CYP2C9*2 and VKORC11639G>A gene polymorphisms to study the genetic factors. INR stability % index was calculated, accordingly patients were classified into 2 groups, stable and unstable groups. Results: The frequencies of VKORC11639G>A alleles in Sudanese out-patients who were on long term warfarin therapy were 70.3% and 29.7% for the VKORC1/G and VKORC1/A alleles respectively. The frequencies of CYP2C9*2 alleles in Sudanese out-patients were 92.4% and 7.6% for CYP2C9*1 and CYP2C9*2 alleles respectively. Variables associated with low INR stability were VKCOR1/AA genotype (p-value = 0.028) and sex (p = 0.017). Variables that showed no association with INR stability were age (p-value = 0.259), compliance (p-value = 0.058). Vitamin K rich foods intake (p-value = 0.743), and mean stable warfarin dose (p-value = 0.439). Conclusion: Polymorphism in warfarin drug target gene VKORC1-11639G>A and sex are important elements of INR stability in Sudanese out-patients on long term warfarin therapy.

show abstract

“…The following studies highlight novel discoveries that can be made, even in relatively small minority cohorts, by leveraging the genomics of non‐Europeans. A study of an Indian population showed the risk allele frequency of CYP4F2*3 (rs2108622) was higher in North Indians (30–44%), as compared with African Americans (12%), Europeans (34%), and Hispanics (23%), suggesting higher warfarin dose requirement for stable anticoagulation . A GWAS using an extreme phenotype strategy in African Americans found a novel association between a genetic variant (rs7856096) in FPGS , a gene known to affect folate homeostasis, and lower warfarin dose requirements among African Americans .…”

Section: Pharmacogenomics and Minority Populationsmentioning

confidence: 99%

The Advantages and Challenges of Diversity in Pharmacogenomics: Can Minority Populations Bring Us Closer to Implementation?

Zhang

Zhong

et al. 2019

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

Health disparities exist among minorities in the United States, with differences seen in disease prevalence, mortality, and responses to medications. These differences are multifactorial with genetic variation explaining a portion of this variability. Pharmacogenomics aims to find the effect of genetic variations on drug response, with the goal of optimizing drug therapy and development. Although genome‐wide association studies have been useful in unbiasedly surveying the genome for genetic drivers of clinically relevant phenotypes, most of these studies have been conducted in mainly participants of European and Asian descent, contributing to a growing health disparity in precision medicine. Diversity is important to pharmacogenomic studies, and there may be real advantages to the use of these complex genomes in pharmacogenomics. In this review we will outline some of the advantages and confounders of pharmacogenomics in minorities, describe the role of genetic variation in pharmacologic pathways, and highlight a number of population‐specific findings.

show abstract

Genetic Epidemiology of Pharmacogenetic Variations in CYP2C9 , CYP4F2 and VKORC1 Genes Associated with Warfarin Dosage in the Indian Population

Cited by 34 publications

References 36 publications

Differences inCYP2C9Genotype and Enzyme Activity Between Swedes and Koreans of Relevance for Personalized Medicine: Role of Ethnicity, Genotype, Smoking, Age, and Sex

Differences inCYP2C9Genotype and Enzyme Activity Between Swedes and Koreans of Relevance for Personalized Medicine: Role of Ethnicity, Genotype, Smoking, Age, and Sex

Genetic and Non-Genetic Factors Association with Warfarin Long Term Therapy Stability in Sudan

The Advantages and Challenges of Diversity in Pharmacogenomics: Can Minority Populations Bring Us Closer to Implementation?

Contact Info

Product

Resources

About