RESUMEN
Introducción y objetivos Siguen sin estudio la eficacia y la seguridad del ticagrelor frente al prasugrel en pacientes con síndrome coronario agudo (SCA) según el índice de masa corporal (IMC). Se evaluaron la eficacia y la seguridad del ticagrelor frente a prasugrel en pacientes con SCA según el IMC. Métodos Se agrupó a los pacientes (n=3.987) en 3 categorías: con peso normal (IMC <25; n=1.084), sobrepeso (IMC ≥ 25 <30; n=1.890) y obesidad (IMC ≥ 30; n=1.013). El objetivo primario de eficacia fue la incidencia de muerte por cualquier causa, infarto de miocardio o accidente cerebrovascular a 1 año. El objetivo secundario de seguridad fue la incidencia de hemorragias de tipo 3-5 de la Bleeding Academic Research Consortium a 1 año. Resultados El objetivo primario se produjo en 63 pacientes asignados a ticagrelor y 39 asignados a prasugrel en el grupo de peso normal (el 11,7 frente al 7,5%; HR=1,62; IC95%, 1,09-2,42; p=0,018), 78 pacientes asignados a ticagrelor y 58 asignados a prasugrel en el grupo de sobrepeso (el 8,3 frente al 6,2%; HR=1,36; IC95%, 0,97-1,91; p=0,076) y 43 pacientes asignados a ticagrelor y 37 asignados a prasugrel en el grupo de obesidad (el 8,6 frente al 7,3%; HR=1,18; IC95%, 0,76-1,84; p=0,451). La incidencia de eventos hemorrágicos a 1 año en los pacientes con peso normal (el 6,5 frente al 6,6%; p=0,990), sobrepeso (el 5,6 frente al 5,0%; p=0,566) u obesidad (el 4,4 frente al 2,8%; p=0,219) no difirió entre el ticagrelor y el prasugrel. No hubo una interacción significativa entre el brazo de tratamiento y el IMC en relación con el objetivo primario (pinteracción=0,578) o el secundario (pinteracción=0,596). Conclusiones En pacientes con SCA, el IMC no influyó significativamente en el efecto del tratamiento con ticagrelor en términos de eficacia o seguridad frente al prasugrel (AU)
Introduction and objectives The efficacy and safety of ticagrelor vs prasugrel in patients with acute coronary syndromes (ACS) according to body mass index (BMI) remain unstudied. We assessed the efficacy and safety of ticagrelor vs prasugrel in patients with ACS according to BMI. Methods Patients (n=3987) were grouped into 3 categories: normal weight (BMI <25kg/m2; n=1084), overweight (BMI ≥ 25 to <30kg/m2; n=1890), and obesity (BMI ≥ 30kg/m2; n=1013). The primary efficacy endpoint was the 1 year incidence of all-cause death, myocardial infarction, or stroke. The secondary safety endpoint was the 1 year incidence of Bleeding Academic Research Consortium type 3 to 5 bleeding. Results The primary endpoint occurred in 63 patients assigned to ticagrelor and 39 patients assigned to prasugrel in the normal weight group (11.7% vs 7.5%; HR, 1.62; 95%CI, 1.09-2.42; P=.018), 78 patients assigned to ticagrelor and 58 patients assigned to prasugrel in the overweight group (8.3% vs 6.2%; HR, 1.36; 95%CI, 0.97-1.91; P=.076), and 43 patients assigned to ticagrelor and 37 patients assigned to prasugrel in the obesity group (8.6% vs 7.3%; HR, 1.18; 95%CI, 0.76-1.84; P=.451). The 1-year incidence of bleeding events did not differ between ticagrelor and prasugrel in patients with normal weight (6.5% vs 6.6%; P=.990), overweight (5.6% vs 5.0%; P=.566) or obesity (4.4% vs 2.8%; P=.219). There was no significant treatment arm-by-BMI interaction regarding the primary endpoint (Pint=.578) or secondary endpoint (Pint=.596). Conclusions In patients with ACS, BMI did not significantly impact the treatment effect of ticagrelor vs prasugrel in terms of efficacy or safety (AU)
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Inhibidores de Agregación Plaquetaria/administración & dosificación , Ticagrelor/administración & dosificación , Clorhidrato de Prasugrel/análogos & derivados , Síndrome Coronario Agudo/tratamiento farmacológico , Índice de Masa Corporal , Resultado del TratamientoRESUMEN
There is limited clinical data comparing different P2Y12-receptor inhibitors in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock. The aim of the ISAR-SHOCK registry was to compare the clinical outcome of patients treated with clopidogrel vs prasugrel in this setting. Patients (n=145) with AMI complicated by cardiogenic shock and undergoing primary PCI in two centres (Deutsches Herzzentrum München and Klinikum rechts der Isar, Technical University Munich) between January 2009 and May 2012 were included in this registry. The use of prasugrel for patients within this registry reflected co-morbidities and platelet function testing results during the acute AMI phase. Early outcome at 30-days was reported with regard to all-cause mortality, myocardial infarction (MI), stent thrombosis (ST) and bleeding events. With regard to antiplatelet treatment in the 145 cardiogenic shock patients, 50 patients were initially treated or immediately switched to prasugrel while 95 patients were treated with clopidogrel. All-cause mortality was lower in prasugrel- vs clopidogrel-treated patients (30 % vs 50.5%, HR: 0.51, 95% CI [0.29-0.92], p=0.025). No significant differences in prasugrel- vs clopidogrel-treated patients were observed for the occurrence of MI (p=0.233), ST (p=0.306) or TIMI major bleedings (p=0.571). Results of the ISAR-SHOCK registry suggest that the use of prasugrel in AMI patients complicated by cardiogenic shock might be associated with a lower mortality risk as compared to clopidogrel therapy without increasing the risk of bleeding. These findings, however, need confirmation from specifically designed randomised studies in this high-risk cohort of patients.
Asunto(s)
Plaquetas/efectos de los fármacos , Infarto del Miocardio/terapia , Intervención Coronaria Percutánea , Piperazinas/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Receptores Purinérgicos P2Y12/efectos de los fármacos , Choque Cardiogénico/etiología , Tiofenos/uso terapéutico , Ticlopidina/análogos & derivados , Anciano , Anciano de 80 o más Años , Plaquetas/metabolismo , Clopidogrel , Trombosis Coronaria/sangre , Trombosis Coronaria/etiología , Trombosis Coronaria/prevención & control , Femenino , Alemania , Hemorragia/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/mortalidad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Piperazinas/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Pruebas de Función Plaquetaria , Clorhidrato de Prasugrel , Valor Predictivo de las Pruebas , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Receptores Purinérgicos P2Y12/sangre , Recurrencia , Sistema de Registros , Factores de Riesgo , Choque Cardiogénico/sangre , Choque Cardiogénico/diagnóstico , Choque Cardiogénico/mortalidad , Tiofenos/efectos adversos , Ticlopidina/efectos adversos , Ticlopidina/uso terapéutico , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Adenosina/análogos & derivados , Competencia Económica , Piperazinas/uso terapéutico , Tiofenos/uso terapéutico , Ticlopidina/análogos & derivados , Adenosina/uso terapéutico , Ensayos Clínicos como Asunto , Clopidogrel , Sustitución de Medicamentos , Quimioterapia Combinada , Competencia Económica/estadística & datos numéricos , Humanos , Clorhidrato de Prasugrel , Ticagrelor , Ticlopidina/uso terapéutico , Resultado del TratamientoRESUMEN
In clopidogrel-treated patients undergoing percutaneous coronary intervention (PCI), high platelet reactivity (HPR) is associated with a higher risk for thrombotic events including stent thrombosis (ST). A personalised therapy with selective intensification of treatment may improve HPR patients´ outcome in this setting although recent randomised trials are against this hypothesis. The aim of the ISAR-HPR registry was to assess whether clopidogrel-treated HPR patients benefit from selective intensification of P2Y12 receptor inhibition. For the registry, outcomes were compared between two cohorts. We identified 428 clopidogrel treated HPR patients (AU x min ≥468 on the Multiplate analyser) between 2007-2008 (historical control cohort) without a change of treatment based on platelet function (PF) testing results. Between 2009-2011, we identified 571 HPR patients (guided therapy cohort) and used this information for guidance and selective intensification of P2Y12 receptor directed treatment (reloading with clopidogrel, switch to prasugrel, re-testing) in a setting of routine PF testing. The primary outcome was the composite of death from any cause or ST after 30 days. Major bleeding according to TIMI criteria was also monitored. The incidence of the primary outcome was significantly lower in the guided vs the control cohort (7 [1.2%] vs 16 [3.7%] events; HR 0.32, 95% CI 0.13-0.79; p=0.009). The incidence of major bleeding was numerically but not statistically higher in the guided vs the control cohort (1.9 vs 0.7%; p=0.10). In conclusion, present findings are in support for a PF testing guided antiplatelet therapy with selective intensification of P2Y12 receptor inhibition. The issue of personalised antiplatelet treatment warrants further investigation in randomized and well-controlled clinical trials.
Asunto(s)
Plaquetas/efectos de los fármacos , Trombosis Coronaria/prevención & control , Intervención Coronaria Percutánea , Piperazinas/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Medicina de Precisión , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Tiofenos/uso terapéutico , Ticlopidina/análogos & derivados , Anciano , Anciano de 80 o más Años , Plaquetas/metabolismo , Estudios de Casos y Controles , Clopidogrel , Trombosis Coronaria/etiología , Trombosis Coronaria/mortalidad , Resistencia a Medicamentos , Sustitución de Medicamentos , Femenino , Alemania , Hemorragia/inducido químicamente , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Piperazinas/efectos adversos , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/efectos adversos , Pruebas de Función Plaquetaria , Clorhidrato de Prasugrel , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Receptores Purinérgicos P2Y12/sangre , Receptores Purinérgicos P2Y12/efectos de los fármacos , Sistema de Registros , Factores de Riesgo , Tiofenos/efectos adversos , Ticlopidina/efectos adversos , Ticlopidina/uso terapéutico , Factores de Tiempo , Resultado del TratamientoRESUMEN
Oral anticoagulants and platelet receptor blockers are widely used in clinical practice with the aim of reducing the risk of thrombotic complications in patients with cardiovascular diseases. Their regular intake and adequate antithrombotic action is vital and this is way numerous assays have been developed for laboratory testing and monitoring of these agents. Available assays can be stratified into pharmacokinetic and pharmacodynamic assays. Such assays are increasingly used in clinical routine and their daily use is triggered by the advent of the novel direct oral anticoagulants (DOACs) as an alternative for vitamin K antagonist (VKA) treatment, which are dabigatran, rivaroxaban and apixaban, and by the advent of prasugrel or ticagrelor as an alternative for clopidogrel with regard to platelet P2Y12 receptor inhibition. In this review the most important and most commonly used laboratory assays are summarized as well as their clinical implications with the focus on DOACs as an alternative for VKAs and the different P2Y12 receptor blockers for antiplatelet treatment.
Asunto(s)
Anticoagulantes/administración & dosificación , Anticoagulantes/sangre , Pruebas de Coagulación Sanguínea/métodos , Monitoreo de Drogas/métodos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/sangre , Administración Oral , Relación Dosis-Respuesta a Droga , HumanosRESUMEN
Knowledge of rare but important clinical disease symptoms in cardiology is of vital importance in the daily routine as severe courses of disease as well as death may be prevented by early diagnosis, effective monitoring and timely initiation of an adequate therapy. In this article an important rhythmological disease, arrhythmogenic right ventricular cardiomyopathy, as well as two significant structural diseases, takotsubo (stress-related) cardiomyopathy and aortic aneurysm related to Marfan syndrome, as well as their implications for clinical practice will be presented.
Asunto(s)
Aneurisma de la Aorta/diagnóstico , Aneurisma de la Aorta/terapia , Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/terapia , Síndrome de Marfan/diagnóstico , Cardiomiopatía de Takotsubo/diagnóstico , Cardiomiopatía de Takotsubo/terapia , Diagnóstico Diferencial , Humanos , Síndrome de Marfan/terapia , Enfermedades RarasRESUMEN
Blood platelets are highly activated in the setting of an acute coronary syndrome (ACS). This fact mandates the need for potent platelet inhibition in ACS patients and especially in patients undergoing a percutaneous coronary intervention (PCI). The 2 nd generation thienopyridine clopidogrel has been the standard of treatment in the past. Due to its pharmacological properties including a delayed onset of action, a large response variability and an insufficient antiplatelet action in some patients (low responsiveness or high on-treatment platelet reactivity), there was a need to develop, to study and to introduce more potent agents with a fast, reliable and potent antiplatelet action. With the 3rd generation thienopyridine prasugrel and with ticagrelor two potent agents for antiplatelet treatment of ACS patients are available now. Both drugs have demonstrated their superiority compared to clopidogrel in terms of thrombotic risk reduction in large-scale randomized trials. However, for these agents and in line with the expectations towards a more potent antiplatelet treatment regimen, a higher risk for bleeding was observed for prasugrel and ticagrelor. Further on, the new antiplatelet agents have their own and characteristic contraindications and numerous issues to be considered in clinical practice.This review aims to provide an overview on the state of the art P2Y12 receptor directed inhibition in ACS patients with a focus on patients undergoing a coronary stenting procedure.
Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/metabolismo , Adenosina/análogos & derivados , Piperazinas/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Receptores Purinérgicos P2Y12/metabolismo , Tiofenos/uso terapéutico , Síndrome Coronario Agudo/cirugía , Adenosina/uso terapéutico , Humanos , Agregación Plaquetaria/efectos de los fármacos , Clorhidrato de Prasugrel , Stents , TicagrelorAsunto(s)
Infarto del Miocardio/terapia , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/uso terapéutico , Agregación Plaquetaria/efectos de los fármacos , Fumar/efectos adversos , Ticlopidina/análogos & derivados , Anciano , Anciano de 80 o más Años , Clopidogrel , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/tratamiento farmacológico , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Pruebas de Función Plaquetaria , Fumar/sangre , Stents , Ticlopidina/uso terapéutico , Resultado del TratamientoRESUMEN
The recruitment and activation of blood platelets initiate ischemic events in patients with coronary artery diseases (myocardial infarction). Moreover, platelet activation and aggregation are key events triggering early and late thrombotic complications (stent thromboses) in patients successfully treated with coronary stent implantation. Hence, the inhibition of the thromboxane A2 synthesis by aspirin and the ADP-receptor pathway by clopidogrel have drastically reduced the risk of ischemic complications following coronary stenting. However, clopidogrel has several inherent limitations, including the high incidence of non- or low-responders and the increased risk of bleeding due to the prolonged persistence of its anti-platelet effect. The latter is of particular concern in patients who require non-deferrable surgery. In recent years, novel anti-platelet substances have been clinically evaluated and are now approved for use in patients. These substances offer several potential advantages over the previous strategies and could pave the way for more individualized anti-platelet regimens. In this review, we give an overview on the available clinical data evaluating the benefits of these novel anti-platelet substances.
Asunto(s)
Enfermedad de la Arteria Coronaria/cirugía , Reestenosis Coronaria/prevención & control , Inhibidores de Agregación Plaquetaria/administración & dosificación , Premedicación/tendencias , Stents/efectos adversos , Enfermedad de la Arteria Coronaria/complicaciones , Reestenosis Coronaria/etiología , HumanosRESUMEN
BACKGROUND: With the cytochrome P450 CYP2C19*2 (*2) allelic variant resulting in complete loss of enzyme function and the CYP2C19*17 (*17) variant being linked to increased transcriptional activity with extensive metabolism of CYP2C19 substrates, two common variants of the CYP2C19 gene have been explored recently. Currently, the isolated and interactive impacts of both variants on the antiplatelet effects of chronic clopidogrel therapy are unknown. OBJECTIVES: The aim of this study was to assess the isolated and interactive impacts of *2 and *17 on clopidogrel responsiveness in patients under clopidogrel maintenance treatment. METHODS: Patients (n=986) eligible for this study were under therapy with coronary stent-related chronic treatment with aspirin and clopidogrel. The ADP-induced platelet aggregation was measured on a Multiplate analyzer (in AU*min), and genotypes were determined with a TaqMan assay. RESULTS: Platelet aggregation values were significantly higher in carriers of at least one *2 allele than in homozygous wild-type allele carriers (P<0.001). For *17, platelet aggregation values were significantly lower in carriers of at least one *17 allele than in homozygous wild-type patients (P=0.01). A gene-dose effect was observed for both variants, with a pronounced effect of the mutant allele (*2 or *17) in homozygous patients being seen. For the interactive effect of both variants on platelet aggregation values, a gradual increase in platelet aggregation values was observed from (+)*17/(-)*2 patients, who exhibited the lowest values (median of 207 AU*min) to (-)*17/(-)*2, (+)*17/(+)*2 and (-)*17/(+)*2 patients, who exhibited the highest values (median of 309 AU*min) (P<0.001). CONCLUSIONS: *2 and *17 allele carriage are independent predictors for the antiplatelet effect of chronic clopidogrel therapy.
Asunto(s)
Hidrocarburo de Aril Hidroxilasas/genética , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticlopidina/análogos & derivados , Anciano , Alelos , Aspirina/uso terapéutico , Clopidogrel , Estudios de Cohortes , Citocromo P-450 CYP2C19 , Femenino , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Farmacogenética , Polimorfismo Genético , Stents , Ticlopidina/uso terapéuticoRESUMEN
BACKGROUND: In patients undergoing percutaneous coronary intervention (PCI), a link between bleeding and excess mortality has been demonstrated. A potential association of platelet response to clopidogrel and bleeding has not been well established yet. OBJECTIVES: The aim of the present study was to assess the impact of clopidogrel responsiveness on the risk of bleeding in clopidogrel-treated patients undergoing PCI. METHODS: Patients (n=2533) undergoing PCI after pretreatment with 600 mg of clopidogrel were enrolled in this study. Blood was obtained directly before PCI. Adenosine-diphosphate (ADP)-induced platelet aggregation was assessed on a Multiplate analyzer. The primary endpoint was the incidence of in-hospital Thrombolysis in Myocardial Infarction (TIMI) major bleeding and the secondary endpoint was in-hospital TIMI minor bleeding. Receiver-operator curve (ROC) analysis was used to derive the optimal platelet aggregation value defining enhanced clopidogrel responders for the association of measurements with major bleeding. RESULTS: Thirty-four (1.3%) major bleeding events and 137 (5.4%) minor bleeding events were observed. The risk of a major bleeding was significantly higher in patients (n=975) with an enhanced response to clopidogrel as compared with the remaining patients (n=1558) (2.2 vs. 0.8%, unadjusted odds ratio (OR) 2.6, 95% confidence interval (CI) 1.3-5.2, P=0.005; adjusted OR 3.5, 95% CI 1.6-7.3, P=0.001). No significant differences between both groups were observed for the occurrence of minor bleeding events (P=0.68). CONCLUSIONS: Enhanced clopidogrel responsiveness is associated with a higher risk of major bleeding. Whether guidance of antiplatelet treatment based on platelet function testing proves useful for avoiding bleeding events warrants further investigation.
Asunto(s)
Angioplastia Coronaria con Balón/instrumentación , Enfermedad de la Arteria Coronaria/terapia , Stents Liberadores de Fármacos , Hemorragia/inducido químicamente , Inhibidores de Agregación Plaquetaria/efectos adversos , Agregación Plaquetaria/efectos de los fármacos , Trombosis/prevención & control , Ticlopidina/análogos & derivados , Adenosina Difosfato , Anciano , Angioplastia Coronaria con Balón/efectos adversos , Distribución de Chi-Cuadrado , Clopidogrel , Enfermedad de la Arteria Coronaria/sangre , Femenino , Alemania , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pruebas de Función Plaquetaria , Valor Predictivo de las Pruebas , Curva ROC , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Trombosis/sangre , Trombosis/etiología , Ticlopidina/efectos adversos , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Stents/efectos adversos , Trombosis/tratamiento farmacológico , Ticlopidina/análogos & derivados , Anciano , Anciano de 80 o más Años , Aspirina/uso terapéutico , Clopidogrel , Femenino , Humanos , Masculino , Persona de Mediana Edad , Farmacocinética , Agregación Plaquetaria/efectos de los fármacos , Pruebas de Función Plaquetaria , Trombosis/etiología , Ticlopidina/farmacocinéticaAsunto(s)
Aspirina/farmacología , Plaquetas/efectos de los fármacos , Enfermedad de la Arteria Coronaria/sangre , Complicaciones de la Diabetes/sangre , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Ticlopidina/análogos & derivados , Adenosina Difosfato/farmacología , Anciano , Angioplastia Coronaria con Balón/efectos adversos , Aspirina/uso terapéutico , Clopidogrel , Colágeno/farmacología , Enfermedad de la Arteria Coronaria/terapia , Complicaciones de la Diabetes/terapia , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Humanos , Masculino , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pruebas de Función Plaquetaria , Receptores de Trombina , Trombosis/etiología , Trombosis/prevención & control , Ticlopidina/farmacología , Ticlopidina/uso terapéuticoAsunto(s)
Adenosina Difosfato/metabolismo , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Polimorfismo Genético , Receptores Purinérgicos P2/genética , Ticlopidina/análogos & derivados , Anciano , Clopidogrel , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Receptores Purinérgicos P2Y1 , Ticlopidina/farmacologíaRESUMEN
BACKGROUND: Genetic susceptibility factors for focal idiopathic torsion dystonia (F-ITD) are not established. Mutations in the DYT1 gene can cause focal dystonia, and an association with a polymorphism in the D5 receptor gene (DRD5) has been reported but not confirmed. OBJECTIVE: To investigate a possible role of DYT1 polymorphisms, a CA repeat in the D5 receptor gene (DRD5), the human leukocyte antigen (HLA)-DRB locus, and four polymorphisms in the homocysteine metabolism in the pathogenesis of F-ITD. METHODS: Initially, 100 German patients and 100 matched control subjects were investigated. A second French population with 121 F-ITD patients and matched control subjects was also studied. RESULTS: Two polymorphisms of the beta-cystathionine synthase gene were associated with F-ITD in the German population, but this finding was not replicated in a second independent F-ITD patient and control group of French origin. None of the other investigated polymorphisms was associated with F-ITD. The authors failed to confirm a previously reported association with a polymorphism in DRD5. CONCLUSION: No evidence for an involvement of DYT1, DRD5, HLA-DRB, or polymorphisms in the homocysteine pathway in the pathogenesis of F-ITD was found.