CYP2C9 and VKORC1 genotypes in Puerto Ricans: A case for admixture-matching in clinical pharmacogenetic studies

Villagra, David; Ducongé, Jorge; Windemuth, Andreas; Cadilla, Carmen L.; Kocherla, Mohan; Gorowski, Krystyna; Bogaard, Kali; Renta, Jessica Y.; Cruz, Irelys A.; Mirabal, Sara; Seip, Richard L.; Ruaño, Gualberto

doi:10.1016/j.cca.2010.05.021

Cited by 14 publications

(13 citation statements)

References 34 publications

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“…8 Several single nucleotide polymorphisms (SNPs) in VKORC1 have been associated with a deficiency in vitamin-K dependent clotting factors, resulting in either increased sensitivity to w-arfarin or warfarin resistance. 9 Warfarin inhibits VKORC1 activity by reducing the regeneration of vitamin K and thus exerting its anticoagulation effect. 1,2,7 Reduced vitamin K is the essential cofactor for the activation of clotting factors II, VII, IX and X and proteins C, S and Z by g-glutamyl carboxylase, encoded by GGCX.…”

Section: Introductionmentioning

confidence: 99%

“…10 These alleles can cause alterations in initial warfarin dose sensitivities, delays in achieving a stable maintenance dose, and increased risk of serious or life-threatening bleeding complications. 9 Large body of previous studies on the inter-individual variability of warfarin have demonstrated that the genetic variations in the VKORC1 as well as CYP2C9, a warfarin metabolizing enzyme, influence warfarin responses. 3,4 Moreover, recently it has been revealed that a genetic variation of cytochrome P450 4F2 (CYP4F2) is also associated with a clinically relevant effect of warfarin.…”

Section: Introductionmentioning

confidence: 99%

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Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients

et al. 2011

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Warfarin is a commonly prescribed anticoagulant drug for the prevention of thromboembolic disorders. We investigated the contribution of genetic variations of four genes and clinical factors to warfarin dose requirement and provided a warfarin-dosing algorithm based on genetic and clinical variables in Korean patients. We recruited 564 Korean patients on stable anticoagulation. Single nucleotide polymorphisms (SNPs) for the VKORC1, CYP2C9, CYP4F2 and GGCX were analyzed. Using multiple regression analysis, we developed a model to predict the warfarin requirement. The SNPs of VKORC1, CYP2C9, CYP4F2 and GGCX showed significant correlation with warfarin dose. Patients with the 3730AA genotype received significantly higher doses of warfarin than those with the 3730GG (P¼0.0001). For CYP2C9, the highest maintenance dose was observed in the patients with wild-type genotype compared with the variant allele carriers (Po0.0001). The multiple regression model including age, gender, body surface area (BSA), international normalized ratio (INR) and four genetic polymorphisms accounted for 35% of total variations in warfarin dose (R 2 ¼0.3499; Po0.0001). This study shows that age, gender, BSA, INR and VKORC1, CYP2C9 and CYP4F2 polymorphism affect warfarin dose requirements in Koreans. Translation of this knowledge into clinical guidelines for warfarin prescription may contribute to improve the efficacy and safety of warfarin treatment for Korean patients.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients

et al. 2011

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“…Thus, we searched for this information in the articles in our sample. Although the use of ethnicity as an indicator for genotype has been the subject of much criticism (e.g., Suarez-Kurtz et al, 2010;Villagra et al, 2010), it remains that in the context of nutrigenetics research, the notion of ethnicity can provide important information. Indeed, ethnicity may give some indications on the frequency of a given polymorphism, as is the case with lactose intolerance in Asian populations (Lomer et al, 2008).…”

Section: (V) Limitations Resulting From the Complexity Of The Geneticmentioning

confidence: 98%

Are Research Papers Reporting Results from Nutrigenetics Clinical Research a Potential Source of Biohype?

Stenne

Hurlimann

Godard

2012

Accountability in Research

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Nutrigenetics is a promising field, but the achievability of expected benefits is challenged by the methodological limitations that are associated with clinical research in that field. The mere existence of these limitations suggests that promises about potential outcomes may be premature. Thus, benefits claimed in scientific journal articles in which these limitations are not acknowledged might stimulate biohype. This article aims to examine whether nutrigenetics clinical research articles are a potential source of biohype. Of the 173 articles identified, 16 contained claims in which clinical applications were extrapolated from study results. The methodological limitations being incompletely acknowledged, these articles could potentially be a source of biohype.

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“…[68]], but also within such populations or groups [e.g. [69,70]]. ‘Therefore, before appropriate genotyping panels can be established, the extent of functional genetic variation in candidate genes needs to be determined, especially in understudied populations’ [[71], p. 340].…”

Section: Discussionmentioning

confidence: 99%

Inclusion and Exclusion in Nutrigenetics Clinical Research: Ethical and Scientific Challenges

Hurlimann

Stenne²,

Menuz³

et al. 2011

Lifestyle Genomics

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Background/Aims: There are compelling reasons to ensure the participation of ethnic minorities and populations of all ages worldwide in nutrigenetics clinical research. If findings in such research are valid for some individuals, groups, or communities, and not for others, then ethical questions of justice – and not only issues of methodology and external validity – arise. This paper aims to examine inclusion in nutrigenetics clinical research and its scientific and ethical challenges. Methods: In total, 173 publications were identified through a systematic review of clinical studies in nutrigenetics published between 1998 and 2007. Data such as participants’ demographics as well as eligibility criteria were extracted. Results: There is no consistency in the way participants’ origins (ancestry, ethnicity, or race) and ages are described in publications. A vast majority of the studies identified was conducted in North America and Europe and focused on ‘white’ participants. Our results show that pregnant women (and fetuses), minors, and the elderly (≧75 years old) remain underrepresented. Conclusion: Representativeness in nutrigenetics research is a challenging ethical and scientific issue. Yet, if nutrigenetics is to benefit whole populations and be used in public and global health agendas, fair representation as well as clear descriptions of participants in publications are crucial.

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CYP2C9 and VKORC1 genotypes in Puerto Ricans: A case for admixture-matching in clinical pharmacogenetic studies

Cited by 14 publications

References 34 publications

Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients

Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients

Are Research Papers Reporting Results from Nutrigenetics Clinical Research a Potential Source of Biohype?

Inclusion and Exclusion in Nutrigenetics Clinical Research: Ethical and Scientific Challenges

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