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European Review For Medical and... 2015This study reviews the available data from randomized controlled trials on efficacy and safety of LCI699, a novel inhibitor of aldosterone synthase, as treatment of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study reviews the available data from randomized controlled trials on efficacy and safety of LCI699, a novel inhibitor of aldosterone synthase, as treatment of hypertension.
MATERIALS AND METHODS
We performed a meta-analysis of phase II randomized, controlled trials comparing the efficacy/safety of LCI699 with placebo in hypertension patients. For this purpose, PubMed, Embase, Cochrane Library database, ISI-Science Citation Index, and the Chinese Biomedicine Literature Database were searched until August 2013. The available data on mean sitting systolic blood pressure (MSSBP), mean sitting diastolic blood pressure (MSDBP), adverse effects, renin-angiotensin-aldosterone system biomarkers (RAASB) and adrenocorticotropic hormone-stimulated cortisol concentration (AHSC) were collected. All data were analyzed using Review Manager, version 5.2.
RESULTS
The present study finally included three randomized controlled trials, comprising of 623 patients in total. The daily use of ≥ 1 mg LCI699 was associated with a significant reduction of MSSBP (Weighted mean difference/WMD = -8.80, 95% CI: -11.31 to -5.68, p < 0.00001, I2 = 0%) and MSDBP (WMD = -4.94, 95% CI: -7.49 to -2.40, p = 0.00001, I2 = 9%). Adverse reactions occurred in 73 of the 139 patients (52.51%) treated with LCI699 and in 34 of the 63 patients (53.96%) treated with placebo. Pooled meta-analysis showed that the use of LCI699 was associated with no increased risk of side effects compared with placebo (RR = 0.90; 95% CI: 0.68 to 1.18, p = 0.43, I2 = 0%). Suppression of plasma aldosterone was measured at all doses of LCI699 treatment groups. LCI699 suppressed the ACTH-stimulated cortisol response in a dose- and time-dependent manner.
CONCLUSIONS
Current evidence indicates that the novel aldosterone inhibitor LCI699 is an effective and well-tolerated antihypertensive agent that lowers plasma aldosterone concentration and produces a mild ACTH-stimulated cortisol response suppressive effect.
Topics: Adult; Antihypertensive Agents; Clinical Trials, Phase II as Topic; Cytochrome P-450 CYP11B2; Female; Humans; Hypertension; Imidazoles; Multicenter Studies as Topic; Pyridines; Randomized Controlled Trials as Topic
PubMed: 25683946
DOI: No ID Found -
Inflammation Research : Official... Mar 2016A systematic review of all literature was done to assess the ability of the progestin dienogest (DNG) to influence the inflammatory response of endometriotic cells. (Review)
Review
OBJECTIVE AND DESIGN
A systematic review of all literature was done to assess the ability of the progestin dienogest (DNG) to influence the inflammatory response of endometriotic cells.
MAIN OUTCOME MEASURES
In vitro and in vivo studies report an influence of DNG on the inflammatory response in eutopic or ectopic endometrial tissue (animal or human).
RESULTS
After strict inclusion criteria were satisfied, 15 studies were identified that reported a DNG influence on the inflammatory response in endometrial tissue. These studies identified a modulation of prostaglandin (PG) production and metabolism (PGE2, PGE2 synthase, cyclo-oxygenase-2 and microsomal PGE synthase-1), pro-inflammatory cytokine and chemokine production [interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, monocyte chemoattractant protein-1 and stromal cell-derived factor-1], growth factor biosynthesis (vascular endothelial growth factor and nerve growth factor) and signaling kinases, responsible for the control of inflammation. Evidence supports a progesterone receptor-mediated inhibition of the inflammatory response in PR-expressing epithelial cells. It also indicated that DNG inhibited the inflammatory response in stromal cells, however, whether this was via a PR-mediated mechanism is not clear.
CONCLUSIONS
DNG has a significant effect on the inflammatory microenvironment of endometriotic lesions that may contribute to its clinical efficacy. A better understanding of the specific anti-inflammatory activity of DNG and whether this contributes to its clinical efficacy can help develop treatments that focus on the inhibition of inflammation while minimizing hormonal modulation.
Topics: Animals; Cytokines; Endometriosis; Epithelial Cells; Female; Hormone Antagonists; Humans; Immunologic Factors; Intercellular Signaling Peptides and Proteins; Nandrolone; Prostaglandins; Stromal Cells
PubMed: 26650031
DOI: 10.1007/s00011-015-0909-7 -
The Cochrane Database of Systematic... Jun 2015Preterm birth is a major cause of perinatal mortality and morbidity. Cyclo-oxygenase (COX) inhibitors inhibit uterine contractions, are easily administered and appear to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Preterm birth is a major cause of perinatal mortality and morbidity. Cyclo-oxygenase (COX) inhibitors inhibit uterine contractions, are easily administered and appear to have few maternal side effects. However, adverse effects have been reported in the fetus and newborn as a result of exposure to COX inhibitors.
OBJECTIVES
To assess the effects on maternal and neonatal outcomes of COX inhibitors administered as a tocolytic agent to women in preterm labour when compared with (i) placebo or no intervention and (ii) other tocolytics. In addition, to compare the effects of non-selective COX inhibitors with COX-2 selective inhibitors.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (24 August 2014). We also contacted recognised experts and searched reference lists of retrieved studies.
SELECTION CRITERIA
All published and unpublished randomised trials in which COX inhibitors were used for tocolysis for women in labour between 20 and 36 completed weeks' gestation.
DATA COLLECTION AND ANALYSIS
Two review authors independently evaluated methodological quality and extracted data. We sought additional information from study authors. Results are presented using risk ratio (RR; dichotomous data) and mean difference (MD; continuous data) with 95% confidence interval (CI). The number needed to treat for benefit (NNTB) and the number needed to treat for harm (NNTH) were calculated for statistically different categorical outcomes.
MAIN RESULTS
With the addition of seven studies with a total of 684 women, this review now includes outcome data from 20 studies including 1509 women. The non-selective COX inhibitor indomethacin was used in 15 studies. The overall quality of the included studies was considered moderate to low.Three small studies (102 women), two of which were conducted in the 1980's, compared COX inhibition (indomethacin only) with placebo. No difference was shown in birth less than 48 hours after trial entry (average RR 0.20, 95% CI 0.03 to 1.28; two studies with 70 women). Indomethacin resulted in a reduction in preterm birth (before completion of 37 weeks of gestation) in one small study (36 women) (RR 0.21, 95% CI 0.07 to 0.62; NNTB 2, 95% CI 2 to 4); and an increase in gestational age at birth (average MD 3.59 weeks, 95% CI 0.65 to 6.52; two studies with 66 women) and birthweight (MD 716.34 g, 95% CI 425.52 to 1007.16; two studies with 67 infants). No difference was shown in measures of neonatal morbidity or neonatal mortality.Compared with betamimetics, COX inhibitors resulted in a reduction in birth less than 48 hours after trial entry (RR 0.27, 95% CI 0.08 to 0.96; NNTB 7, 95% CI 6 to 120; two studies with 100 women) and preterm birth (before completion of 37 weeks of gestation) (RR 0.53, 95% CI 0.28 to 0.99; NNTB 6, 95% CI 4 to 236; two studies with 80 women) although no benefit was shown in terms of neonatal morbidity or mortality. COX inhibition was also associated with fewer maternal adverse affects compared with betamimetics (RR 0.19, 95% CI 0.11 to 0.31; NNTB 3, 95% CI 2 to 3; five studies with 248 women) and maternal adverse effects requiring cessation of treatment (average RR 0.09, 95% CI 0.02 to 0.49; NNTB 5, CI 95% 5 to 9; three studies with 166 women).No differences were shown when comparing COX inhibitors with magnesium sulphate (MgSO4) (seven studies with 792 women) or calcium channel blockers (CCBs) (two studies with 230 women) in terms of prolonging pregnancy or for any fetal/neonatal outcomes. There were also no differences in very preterm birth (before completion of 34 weeks of gestation) and no maternal deaths occurred in the one study that reported on this outcome. However COX inhibitors resulted in fewer maternal adverse affects when compared with MgSO4 (RR 0.39, 95% CI 0.25 to 0.62; NNTB 11, 95% CI 9 to 17; five studies with 635 women).A comparison of non-selective COX inhibitors versus any COX-2 inhibitor (two studies with 54 women) did not demonstrate any differences in maternal, fetal or neonatal outcomes.No data were available to assess COX inhibitors compared with oxytocin receptor antagonists (ORAs). Further, no data were available on extremely preterm birth (before 28 weeks of gestation), longer-term infant outcomes or costs.
AUTHORS' CONCLUSIONS
In this review, no clear benefit for COX inhibitors was shown over placebo or any other tocolytic agents. While some benefit was demonstrated in terms of postponement of birth for COX inhibitors over placebo and betamimetics and also maternal adverse effects over betamimetics and MgSO4, due to the limitations of small numbers, minimal data on safety, lack of longer-term outcomes and generally low quality of the studies included in this review, we conclude that there is insufficient evidence on which to base decisions about the role of COX inhibition for women in preterm labour. Further well-designed tocolytic studies are required to determine short- and longer-term infant benefit of COX inhibitors over placebo and other tocolytics, particularly CCBs and ORAs. Another important focus for future studies is identifying whether COX-2 inhibitors are superior to non-selective COX inhibitors. All future studies on tocolytics for women in preterm labour should assess longer-term effects into early childhood and also costs.
Topics: Calcium Channel Blockers; Cyclooxygenase Inhibitors; Female; Humans; Indomethacin; Magnesium Sulfate; Pregnancy; Premature Birth; Randomized Controlled Trials as Topic; Tocolytic Agents
PubMed: 26042617
DOI: 10.1002/14651858.CD001992.pub3 -
Neural Regeneration Research Dec 2024The search for reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis, to detect neurodegeneration from the prodromal phase and...
The search for reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis, to detect neurodegeneration from the prodromal phase and to enforce disease-modifying therapies. Despite the need for non-invasively accessible biomarkers, the majority of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers, which require invasive collection procedures. Saliva represents an easily accessible biofluid and an incredibly wide source of molecular biomarkers. In the present study, after presenting the morphological and biological bases for looking at saliva in the search of biomarkers for Parkinson's disease, we systematically reviewed the results achieved so far in the saliva of different cohorts of Parkinson's disease patients. A comprehensive literature search on PubMed and SCOPUS led to the discovery of 289 articles. After screening and exclusion, 34 relevant articles were derived for systematic review. Alpha-synuclein, the histopathological hallmark of Parkinson's disease, has been the most investigated Parkinson's disease biomarker in saliva, with oligomeric alpha-synuclein consistently found increased in Parkinson's disease patients in comparison to healthy controls, while conflicting results have been reported regarding the levels of total alpha-synuclein and phosphorylated alpha-synuclein, and few studies described an increased oligomeric alpha-synuclein/total alpha-synuclein ratio in Parkinson's disease. Beyond alpha-synuclein, other biomarkers targeting different molecular pathways have been explored in the saliva of Parkinson's disease patients: total tau, phosphorylated tau, amyloid-β1-42 (pathological protein aggregation biomarkers); DJ-1, heme-oxygenase-1, metabolites (altered energy homeostasis biomarkers); MAPLC-3beta (aberrant proteostasis biomarker); cortisol, tumor necrosis factor-alpha (inflammation biomarkers); DNA methylation, miRNA (DNA/RNA defects biomarkers); acetylcholinesterase activity (synaptic and neuronal network dysfunction biomarkers); Raman spectra, proteome, and caffeine. Despite a few studies investigating biomarkers targeting molecular pathways different from alpha-synuclein in Parkinson's disease, these results should be replicated and observed in studies on larger cohorts, considering the potential role of these biomarkers in determining the molecular variance among Parkinson's disease subtypes. Although the need for standardization in sample collection and processing, salivary-based biomarkers studies have reported encouraging results, calling for large-scale longitudinal studies and multicentric assessments, given the great molecular potentials and the non-invasive accessibility of saliva.
PubMed: 38595280
DOI: 10.4103/NRR.NRR-D-23-01677 -
BMJ (Clinical Research Ed.) May 2017To characterise the determinants, time course, and risks of acute myocardial infarction associated with use of oral non-steroidal anti-inflammatory drugs... (Meta-Analysis)
Meta-Analysis Review
To characterise the determinants, time course, and risks of acute myocardial infarction associated with use of oral non-steroidal anti-inflammatory drugs (NSAIDs). Systematic review followed by a one stage bayesian individual patient data meta-analysis. Studies from Canadian and European healthcare databases. Eligible studies were sourced from computerised drug prescription or medical databases, conducted in the general or an elderly population, documented acute myocardial infarction as specific outcome, studied selective cyclo-oxygenase-2 inhibitors (including rofecoxib) and traditional NSAIDs, compared risk of acute myocardial infarction in NSAID users with non-users, allowed for time dependent analyses, and minimised effects of confounding and misclassification bias. Drug exposure was modelled as an indicator variable incorporating the specific NSAID, its recency, duration of use, and dose. The outcome measures were the summary adjusted odds ratios of first acute myocardial infarction after study entry for each category of NSAID use at index date (date of acute myocardial infarction for cases, matched date for controls) versus non-use in the preceding year and the posterior probability of acute myocardial infarction. A cohort of 446 763 individuals including 61 460 with acute myocardial infarction was acquired. Taking any dose of NSAIDs for one week, one month, or more than a month was associated with an increased risk of myocardial infarction. With use for one to seven days the probability of increased myocardial infarction risk (posterior probability of odds ratio >1.0) was 92% for celecoxib, 97% for ibuprofen, and 99% for diclofenac, naproxen, and rofecoxib. The corresponding odds ratios (95% credible intervals) were 1.24 (0.91 to 1.82) for celecoxib, 1.48 (1.00 to 2.26) for ibuprofen, 1.50 (1.06 to 2.04) for diclofenac, 1.53 (1.07 to 2.33) for naproxen, and 1.58 (1.07 to 2.17) for rofecoxib. Greater risk of myocardial infarction was documented for higher dose of NSAIDs. With use for longer than one month, risks did not appear to exceed those associated with shorter durations. All NSAIDs, including naproxen, were found to be associated with an increased risk of acute myocardial infarction. Risk of myocardial infarction with celecoxib was comparable to that of traditional NSAIDS and was lower than for rofecoxib. Risk was greatest during the first month of NSAID use and with higher doses.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Bayes Theorem; Canada; Dose-Response Relationship, Drug; Europe; Humans; Myocardial Infarction
PubMed: 28487435
DOI: 10.1136/bmj.j1909 -
BioMed Research International 2020Clozapine is a second-generation antipsychotic drug that is considered the most effective treatment for refractory schizophrenia. Several clozapine population...
BACKGROUND AND OBJECTIVE
Clozapine is a second-generation antipsychotic drug that is considered the most effective treatment for refractory schizophrenia. Several clozapine population pharmacokinetic models have been introduced in the last decades. Thus, a systematic review was performed (i) to compare published pharmacokinetics models and (ii) to summarize and explore identified covariates influencing the clozapine pharmacokinetics models.
METHODS
A search of publications for population pharmacokinetic analyses of clozapine either in healthy volunteers or patients from inception to April 2019 was conducted in PubMed and SCOPUS databases. Reviews, methodology articles, in vitro and animal studies, and noncompartmental analysis were excluded.
RESULTS
Twelve studies were included in this review. Clozapine pharmacokinetics was described as one-compartment with first-order absorption and elimination in most of the studies. Significant interindividual variations of clozapine pharmacokinetic parameters were found in most of the included studies. Age, sex, smoking status, and cytochrome P450 1A2 were found to be the most common identified covariates affecting these parameters. External validation was only performed in one study to determine the predictive performance of the models.
CONCLUSIONS
Large pharmacokinetic variability remains despite the inclusion of several covariates. This can be improved by including other potential factors such as genetic polymorphisms, metabolic factors, and significant drug-drug interactions in a well-designed population pharmacokinetic model in the future, taking into account the incorporation of larger sample size and more stringent sampling strategy. External validation should also be performed to the previously published models to compare their predictive performances.
Topics: Adult; Antipsychotic Agents; Clozapine; Cytochrome P-450 CYP1A2; Female; Humans; Male; Middle Aged; Models, Biological; Schizophrenia
PubMed: 31998804
DOI: 10.1155/2020/9872936 -
Cardiovascular Therapeutics Feb 2017To assess the effect of Cytochrome P450 2C9 (CYP2C9) gene polymorphism on pediatric warfarin maintenance dosage requirement. (Meta-Analysis)
Meta-Analysis Review
AIM
To assess the effect of Cytochrome P450 2C9 (CYP2C9) gene polymorphism on pediatric warfarin maintenance dosage requirement.
METHODS
A previously developed search strategy was conducted in PubMed, EMBASE, and the Cochrane Library. Eligible studies published prior to January 27, 2016, were identified and compared against strict inclusion/exclusion criteria. Required data were extracted, and researchers were consulted for additional data if needed. Review Manager version 5.2.3 software was used to analyze the relationship between CYP2C9 polymorphisms and warfarin maintenance doses in pediatric patients. Eight articles with a combined total of 507 pediatric patients were included in the meta-analysis.
RESULTS
Maintenance warfarin doses in patients with CYP2C9 *1/*2 genotype, CYP2C9 *1/*3 genotype, and CYP2C9 variant carriers which contain at least one variant allele (*2 or *3) were from 15% to 41% lower than doses in patients with the wild-type allele (CYP2C9 *1/*1): All differences were significant with P-values <.05. The Fontan procedure as a medical indication for anticoagulation was also associated with a lower warfarin maintenance dose; however, target INR range was not.
CONCLUSIONS
We found that CYP2C9 gene polymorphism (referring to the presence of *1/*2, *1/*3, and variant genotypes in the population in addition to the wild type) was significantly associated with decreased warfarin maintenance dose requirements. Additionally, a specific indication for warfarin, the Fontan procedure, was associated with a lower daily warfarin dose. However, the results of our study require confirmation from more research with larger numbers of pediatric patients.
Topics: Adolescent; Age Factors; Anticoagulants; Blood Coagulation; Chi-Square Distribution; Child; Child, Preschool; Cytochrome P-450 CYP2C9; Drug Dosage Calculations; Female; Genotype; Humans; Infant; International Normalized Ratio; Male; Pharmacogenetics; Pharmacogenomic Variants; Phenotype; Polymorphism, Genetic; Warfarin; Young Adult
PubMed: 27661060
DOI: 10.1111/1755-5922.12230 -
Journal of Sport and Health Science Jul 2024The ergogenic effects of caffeine intake on exercise performance are well-established, even if differences exist among individuals in response to caffeine intake. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The ergogenic effects of caffeine intake on exercise performance are well-established, even if differences exist among individuals in response to caffeine intake. The genetic variation of a specific gene, human cytochrome P450 enzyme 1A2 (CYP1A2) (rs762551), may be one reason for this difference. This systematic review and meta-analysis aimed to comprehensively evaluate the influence of CYP1A2 gene types on athletes' exercise performance after caffeine intake.
METHODS
A literature search through 4 databases (Web of Science, PubMed, Scopus, and China National Knowledge Infrastructure) was conducted until March 2023. The effect size was expressed as the weighted mean difference (WMD) by calculating fixed effects meta-analysis if heterogeneity was not significant (I ≤ 50% and p ≥ 0.1). Subgroup analyses were performed based on AA and AC/CC genotype of CYP1A2.
RESULTS
The final number of studies meeting the inclusion criteria was 12 (n = 666 participants). The overall analysis showed that the cycling time trial significantly improved after caffeine intake (WMD = -0.48, 95% confidence interval (95%CI): -0.83 to -0.13, p = 0.007). In subgroup analyses, acute caffeine intake improved cycling time trial only in individuals with the A allele (WMD = -0.90, 95%CI: -1.48 to -0.33, p = 0.002), but not the C allele (WMD = -0.08, 95%CI: -0.32 to 0.17, p = 0.53). Caffeine supplementation did not influence the Wingate (WMD = 8.07, 95%CI: -22.04 to 38.18, p = 0.60) or countermovement jump test (CMJ) performance (WMD = 1.17, 95%CI: -0.02 to 2.36, p = 0.05), and these outcomes were not influenced by CYP1A2 genotype.
CONCLUSION
Participants with the CYP1A2 genotype with A allele improved their cycling time trials after caffeine supplementation. However, compared to placebo, acute caffeine supplementation failed to increase the Wingate or CMJ performance, regardless of CYP1A2 genotype.
Topics: Cytochrome P-450 CYP1A2; Humans; Caffeine; Athletic Performance; Performance-Enhancing Substances; Genotype; Dietary Supplements; Bicycling
PubMed: 38158179
DOI: 10.1016/j.jshs.2023.12.005 -
Journal of Thrombosis and Haemostasis :... Sep 2014Although warfarin and other vitamin K antagonists (VKAs) are the most widely used oral anticoagulants for the prevention and treatment of thromboembolic events, a number... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although warfarin and other vitamin K antagonists (VKAs) are the most widely used oral anticoagulants for the prevention and treatment of thromboembolic events, a number of factors hamper their manageability, the most important being the inter-individual variability of the therapeutic dose requirement. Following the discovery of the influence of CYP2C9 and VKORC1 polymorphisms on VKA dose requirements, there has been interest in genotype-guided VKA dosing in order to reduce the risk of over-anticoagulation at the time of therapy initiation and hence the risk of bleeding, particularly prominent during the early days of treatment. To assess the impact on clinical outcomes of pharmacogenetic testing for initial VKA dosing, we have performed a systematic review and meta-analysis of the literature.
METHODS
MEDLINE, EMBASE and Cochrane databases were searched up to March 2014. Only randomized controlled trials comparing genotype-guided vs. clinically-guided warfarin dosing were included.
RESULTS
Nine trials including 2812 patients met the inclusion criteria and were pooled for meta-analytical evaluation. Risk of bias, assessed according to the Cochrane methodology, showed a low risk for the majority of domains analyzed in the included trials. A statistically significant reduction in the risk ratio (RR) for developing major bleeding events was observed in the pharmacogenetic-guided group compared with the control group (RR = 0.47; 95% CI, 0.23-0.96; P = 0.040).
CONCLUSIONS
The results of this meta-analysis show that genotype-guided initial VKA dosing is able to reduce serious bleeding events by approximately 50% compared with clinically-guided dosing approaches.
Topics: Adult; Aged; Anticoagulants; Blood Coagulation; Cytochrome P-450 CYP2C9; Female; Genotype; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Pharmacogenetics; Prospective Studies; Randomized Controlled Trials as Topic; Reproducibility of Results; Thromboembolism; Treatment Outcome; Vitamin K; Vitamin K Epoxide Reductases; Warfarin
PubMed: 25040440
DOI: 10.1111/jth.12647 -
PloS One 2016Warfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in... (Review)
Review
BACKGROUND
Warfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in CYP2C9 and VKORC1 genes are strongly and consistently associated with warfarin dose variability. Although different populations from the Middle East and North Africa (MENA) region may share the same ancestry, it is still unclear how they compare in the genetic and non-genetic factors affecting their warfarin dosing.
OBJECTIVE
To explore the prevalence of CYP2C9 and VKORC1 variants in MENA, and the effect of these variants along with other non-genetic factors in predicting warfarin dose.
METHODS
In this systematic review, we included observational cross sectional and cohort studies that enrolled patients on stable warfarin dose and had the genetics and non-genetics factors associated with mean warfarin dose as the primary outcome. We searched PubMed, Medline, Scopus, PharmGKB, PHGKB, Google scholar and reference lists of relevant reviews.
RESULTS
We identified 17 studies in eight different populations: Iranian, Israeli, Egyptian, Lebanese, Omani, Kuwaiti, Sudanese and Turkish. Most common genetic variant in all populations was the VKORC1 (-1639G>A), with a minor allele frequency ranging from 30% in Egyptians and up to 52% and 56% in Lebanese and Iranian, respectively. Variants in the CYP2C9 were less common, with the highest MAF for CYP2C9*2 among Iranians (27%). Variants in the VKORC1 and CYP2C9 were the most significant predictors of warfarin dose in all populations. Along with other genetic and non-genetic factors, they explained up to 63% of the dose variability in Omani and Israeli patients.
CONCLUSION
Variants of VKORC1 and CYP2C9 are the strongest predictors of warfarin dose variability among the different populations from MENA. Although many of those populations share the same ancestry and are similar in their warfarin dose predictors, a population specific dosing algorithm is needed for the prospective estimation of warfarin dose.
Topics: Africa, Northern; Cytochrome P-450 CYP2C9; Female; Genetic Variation; Humans; Male; Middle East; Pharmacogenomic Testing; Vitamin K Epoxide Reductases; Warfarin
PubMed: 27992547
DOI: 10.1371/journal.pone.0168732