Influence of genetic and non-genetic factors on acenocoumarol maintenance dose requirement in a Tunisian population

Ajmi, Mohamed; Omezzine, Asma; Achour, Slim; Amor, Dorra; Hamdouni, Haithem; Ismail, F. Ben Fredj; Rejeb, N.; Kechrid, C. Laouani; Boughzéla, Essia; Bouslama, Ali

doi:10.1007/s00228-018-2423-7

Cited by 8 publications

(4 citation statements)

References 60 publications

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“…Based on these findings, we can hypothesize that the ancestral "C" allele is a protective allele for the Tunisian patients against hemorrhagic complications caused by an overdose of acenocoumarol. Our results oppose those of Ajmi et al who declared the protective effect of rs7294 "T" allele against bleeding caused by acenocoumarol treatment 53 . This study was conducted on 246 Tunisian patients who originated from the Sahel region.…”

Section: Discussioncontrasting

confidence: 99%

Genetic diversity of variants involved in drug response among Tunisian and Italian populations toward personalized medicine

Jmel,

Sarno,

Giuliani

et al. 2024

Sci Rep

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Adverse drug reactions (ADR) represent a significant contributor to morbidity and mortality, imposing a substantial financial burden. Genetic ancestry plays a crucial role in drug response. The aim of this study is to characterize the genetic variability of selected pharmacogenes involved with ADR in Tunisians and Italians, with a comparative analysis against global populations. A cohort of 135 healthy Tunisians and 737 Italians were genotyped using a SNP array. Variants located in 25 Very Important Pharmacogenes implicated in ADR were extracted from the genotyping data. Distribution analysis of common variants in Tunisian and Italian populations in comparison to 24 publicly available worldwide populations was performed using PLINK and R software. Results from Principle Component and ADMIXTURE analyses showed a high genetic similarity among Mediterranean populations, distinguishing them from Sub-Saharan African and Asian populations. The Fst comparative analysis identified 27 variants exhibiting significant differentiation between the studied populations. Among these variants, four SNPs rs622342, rs3846662, rs7294, rs5215 located in SLC22A1, HMGCR, VKORC1 and KCNJ11 genes respectively, are reported to be associated with ethnic variability in drug responses. In conclusion, correlating the frequencies of genotype risk variants with their associated ADRs would enhance drug outcomes and the implementation of personalized medicine in the studied populations.

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Section: Discussioncontrasting

confidence: 99%

Genetic diversity of variants involved in drug response among Tunisian and Italian populations toward personalized medicine

Jmel,

Sarno,

Giuliani

et al. 2024

Sci Rep

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“…44) Age, body weight and BMI have a correlation with the maintenance dose of VKAs. 7,8) Additional research is needed to examine the association between haplotype, ethnicity, age, BMI and weekly doses of VKAs.…”

Section: Discussionmentioning

confidence: 99%

“…VKAs have a narrow therapeutic range and, therefore, levels outside this range increase the risk of thromboem-bolism or bleeding incidences.VKAs are drugs that interact with various medications and foods [4][5][6] and maintenance doses of VKAs are affected by patient age, 7) body weight, 8) clinical conditions, 9,10) and genetic factors. 8,11) According to the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, cytochrome P450 2C9 (CYP2C9), vitamin K epoxide reductase complex subunit 1 (VKORC1), and cytochrome P450 4F2 (CYP4F2) are known to influence the warfarin dosing algorithm. 11) Similarly, the maintenance dose of acenocoumarol is also affected by VKORC1 and CYP2C9 genes.…”

mentioning

confidence: 99%

Impact of ABCB1 C3435T Polymorphism on Treatment Response of Vitamin K Antagonists: A Systematic Review and Meta-analysis

Lee

2022

Korean J Clin Pharm

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In the United States, approximately 2.7-6.1 million patients had atrial fibrillation (AF) in 2010, and this number is expected to gradually increase to approximately 5.6 to 12 million by 2050. 1,2) The vitamin K antagonists (VKAs), warfarin and acenocoumarol, are prescribed for the treatment or prophylaxis of embolic AF or deep vein thrombosis (DVT). Warfarin was commonly prescribed for older individuals, those with a high risk of stroke or bleeding, and patients with many comorbidities. 3) These patients are likely to have drugdisorder or drug-drug interactions. It is necessary for patient safety and personal medication therapy to regularly monitor prothrombin time (PT) or the international normalized ratio (INR). VKAs have a narrow therapeutic range and, therefore, levels outside this range increase the risk of thromboem-bolism or bleeding incidences.VKAs are drugs that interact with various medications and foods [4][5][6] and maintenance doses of VKAs are affected by patient age, 7) body weight, 8) clinical conditions, 9,10) and genetic factors. 8,11) According to the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, cytochrome P450 2C9 (CYP2C9), vitamin K epoxide reductase complex subunit 1 (VKORC1), and cytochrome P450 4F2 (CYP4F2) are known to influence the warfarin dosing algorithm. 11) Similarly, the maintenance dose of acenocoumarol is also affected by VKORC1 and CYP2C9 genes. 12) In addition to these well-known genes, recent studies have suggested that the ATP-binding cassette subfamily B member 1 (ABCB1) gene affects the maintenance dose of VKAs; however, the

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“…Majority of the patients with these variant genotypes were found to belong to a low acenocoumarol dose group [27]. In Tunisia, Ajmi et al demonstrated an association between daily acenocoumarol dose and CYP2C9 (*2, *3) and VKORC1 (H1, H7) haplotypes [28].…”

Section: Cvdsmentioning

confidence: 99%

A Review of Clinical Pharmacogenetics Studies in African Populations

et al. 2020

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Effective interventions and treatments for complex diseases have been implemented globally, however, coverage in Africa has been comparatively lower due to lack of capacity, clinical applicability and knowledge on the genetic contribution to disease and treatment. Currently, there is a scarcity of genetic data on African populations, which have enormous genetic diversity. Pharmacogenomics studies have the potential to revolutionise treatment of diseases, therefore, African populations are likely to benefit from these approaches to identify likely responders, reduce adverse side effects and optimise drug dosing. This review discusses clinical pharmacogenetics studies conducted in African populations, focusing on studies that examined drug response in complex diseases relevant to healthcare. Several pharmacogenetics associations have emerged from African studies, as have gaps in knowledge.

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Influence of genetic and non-genetic factors on acenocoumarol maintenance dose requirement in a Tunisian population

Abstract: The PA demonstrated that VKORC1 and CYP2C9 polymorphisms contribution was more important than clinical factors. Applying the PA would allow dose adjustment to treat patients in a personalized manner.

Cited by 8 publications

References 60 publications

Genetic diversity of variants involved in drug response among Tunisian and Italian populations toward personalized medicine

Genetic diversity of variants involved in drug response among Tunisian and Italian populations toward personalized medicine

Impact of ABCB1 C3435T Polymorphism on Treatment Response of Vitamin K Antagonists: A Systematic Review and Meta-analysis

A Review of Clinical Pharmacogenetics Studies in African Populations

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