Alcohol dehydrogenase 2 genotype and allelic variants are not associated with the risk for essential tremor

OBJECTIVE: To investigate the possible association between alcohol dehydrogenase 1B, beta-polypeptide (ADH2) genotype and allelic variants and the risk for developing essential tremor (ET). METHODS: Leukocytary DNA from 204 ET patients and 200 healthy controls was studied for the genotype ADH2 and the occurrence of ADH2 allelic variants using allele-specific polymerase chain reaction amplification and MslI-restriction fragment length polymorphism's analyses. RESULTS: The frequencies of the ADH2*1/ADH2*2 genotype and of the allelic variant ADH2*2 did not differ significantly in ET patients when compared with those of the controls. The mean age at onset of ET did not differ significantly between patients with genotypes ADH2*1/ADH2*2 and ADH2*1/ADH2*1. The frequencies of the genotype ADH2*1/ADH2*2 and of the allelic variant ADH2*2 in patients with voice, tongue, and chin tremors did not differ from those of the controls, whereas patients with voice tremor showed lower frequencies of mutated genotypes and ADH2*2 alleles. The frequencies of ADH2 genotypes and ADH2 alleles did not differ significantly between patients who did not drink ethanol and those who reported improvement, no improvement, or unknown response of tremor to ethanol. CONCLUSIONS: These results suggest that ADH2 genotype and allelic variants are not associated with the risk for ET in white Spanish people.     

Essential tremor variants: effect of treatment

Essential tremor may not represent a single condition. Subclassifications include kinetic predominant tremor; combined resting-postural tremor; primary writing tremor; isolated voice, chin, or tongue tremor; and orthostatic truncal tremor. We report patients with these disorders. An association of these conditions with essential tremor is suggested by a high occurrence of a family history of essential tremor, frequent presence of a mild postural tremor, and tremor reduction with alcohol ingestion. Pharmacologic responsiveness is different for these disorders. Propranolol and primidone often have beneficial effects but clonazepam was the only drug effective in some cases of kinetic predominant tremor and in orthostatic truncal tremor. Combined resting-postural tremor and voice tremor were often unresponsive to treatment.     

Changes at the CYP2C locus and disruption of CYP2C8/9 linkage disequilibrium in patients with essential tremor

To identify low-penetrance genes related to sporadic essential tremor (ET) at the CYP2Clocus, located in chromosome 10 q23.33. Leukocytary DNA from 200 ET patients and a control group of 300 unrelated healthy individuals with known CYP2C19 genotypes was studied for common CYP2C8 and CYP2C9 allelic variants by using amplification-restriction analyses. Patients with ET showed the following differences compared with healthy subjects: a 1.6-fold reduction in the frequency for CYP2C8*3 (p=0.006), a 1.35-fold reduction of CYP2C9*2 (p=0.05) and a 1.52-fold reduction in the frequency for CYP2C9*3 (p=0.07). The frequency for patients with ET carrying at least one defective allele was 1.33-fold reduced as compared with healthy subjects (p=0.002). In addition, a disruption of the CYP2C8*3/CYP2C9*2 linkage disequilibrium was observed in ET patients, with a 2.1-fold reduction in the percentage for carriers of the haplotype CYP2C8*3 plus CYP2C9*2 in ET patients (p=0.0001). These findings were independent of gender, age, age of onset, or clinical symptoms. These results suggest that alterations at the CYP2C gene locus are associated with the risk for ET.     

Deep brain stimulation of the ventral intermediate thalamic nucleus in the treatment of essential tremor

Essential tremor (ET) is the most common movement disorder. In most patients the course of ET is mild and pharmacological therapy controls postural and kinetic components of tremor. The first-line treatment of ET is pharmacotherapy with propranolol, primidone and gabapentin. In patients with marked head and voice tremor, local botulinum toxin injections have been found to be very effective. Despite optimal drug therapies it is estimated that approximately 50% of patients with ET have medication-resistant tremor. ET can cause more functional impairment than parkinsonian resting tremor because most prominent components of ET are postural and kinetic ones. For patients with drug-resistant debilitating tremor, surgical therapy (thalamotomy) and more recently deep brain stimulation (DBS) of the ventral intermediate thalamic nucleus (VIM) is a viable treatment modality. Several long-term studies have confirmed the high effectiveness rate of ablative surgery and thalamic DBS in the treatment of ET. The most striking advantage of thalamic DBS is the possibility of performing bilateral surgery in one operative session with a significantly lower rate of side effects. Nowadays the bilateral staged thalamotomy is performed rarely because of unacceptable side effects. Moreover, many authors have observed that in bilaterally stimulated patients the head and voice tremor have diminished in postoperative course. Thalamic DBS is a very efficacious and safe procedure in the treatment of ET.     

Glutathione-S-transferase P1 polymorphism and risk for essential tremor

Glutathione- S -transferases (GST) are polymorphic enzymes that participate in the metabolism of carcinogens (including those of tobacco smoke) and pesticides. We investigated the possible association between the GSTP1 genotype and allelic variants and the risk for essential tremor (ET). We studied the frequency of the GSTP1 genotypes and allelic variants in 200 patients with ET and 220 healthy controls using PCR-RFLP method. The association between GSTP1 polymorphism and the exposure to some environmental factors (agricultural work, pesticides, well-water and smoking-cigarettes habit) was also studied in a subgroup of patients. The frequencies of the GSTP1 genotypes and allelic variants did not differ significantly between patients with ET and controls or between patients with ET exposed to agricultural work, well water and cigarette smoking versus those non-exposed. Mutated allelic variants were significantly more frequent in patients with ET exposed to pesticides versus those non-exposed. GSTP1 polymorphism was unrelated with the age of onset of ET. GSTP1 genotypes and allelic variants were not related with the risk for ET with the possible exception of those patients exposed to pesticides.     

Acute and chronic effects of propranolol and primidone in essential tremor

We studied the acute and chronic effects of propranolol and primidone in essential tremor by administering long-acting propranolol (80 to 160 mg/d) and primidone (50 to 250 mg/d) to 50 patients. We evaluated patients at 1, 3, 6, 9, and 12 months after treatment and assessed tremor by subjective rating by patients, clinical scoring, and thermographic (accelerometer) recordings. Acute adverse reactions occurred in 8% with propranolol and 32% with primidone. Propranolol was without therapeutic effect in 30%, and 32% had no benefit from primidone. Significant chronic side effects occurred in 17% taking propranolol and in 0% with primidone. Tolerance to drug effect occurred with chronic treatment in 12.5% of patients with propranolol and 13.0% with primidone. We conclude that propranolol and primidone are effective long-term treatment for some patients with essential tremor. Acute adverse reactions with primidone and side effects with chronic use of propranolol hamper therapy.     

Essential tongue tremor

Twenty patients with tongue tremor associated with essential tremor are reported. Patients were unaware of the tongue tremor, and voice disturbance was a complaint in only one patient. Three patients had an isolated tongue tremor. Hand tremor was present in 16 patients. Dystonia, myoclonus, and tremor of other body parts were present in some patients. Three patients had a mild-to-moderate dysarthria. The frequency of tongue tremor (4-8 Hz) was identical to hand tremor. The intravenous infusion of ethanol suppressed tongue tremor. Therapy with propranolol, primidone, or clonazepam also reduced tongue tremor amplitude. Tongue tremor is a common finding in some essential tremor patients but often there are no symptoms.     

Paraoxonase 1 (PON1) polymorphisms and risk for essential tremor

Background: The polymorphic enzyme human serum paraoxonase 1 (PON1), encoded by the gene PON1 (chromosome 7q21.3), plays a major role in the metabolism of organophosphorus compounds. We investigated the possible association between the PON1 genotype and allelic variants of the polymorphisms Leu55Met and Glu192Arg, and the risk for essential tremor (ET). Methods: We studied the frequency of the PON1 genotypes and allelic variants in 201 patients with ET and 220 healthy controls using a PCR‐RLFP method. Results: The frequencies of the PON1 genotypes and allelic variants of the polymorphisms Leu55Met and Gln192Arg did not differ significantly between patients with ET and controls. These polymorphisms were unrelated with the age of onset of ET. Conclusions: PON1 polymorphisms are not related with the risk for ET.     

Report on IL-10 gene polymorphism at position -819 for major depression and schizophrenia in Korean population

The present study was carried out to examine the relationship of interleukin (IL)-10 gene polymorphism at position -819 for major depression and schizophrenia in the Korean population. DNA was extracted from 92 Korean patients with major depression, 141 Korean patients with schizophrenia, and 146 ethnically matched controls. DNA was amplified by a polymerase chain reaction-based method and digested by MaeIII, and the restriction fragment length polymorphism of two alleles, IL-10*C and IL-10*T, were assessed. There were no significant differences in genotype frequencies of IL-10*T/T, IL-10*T/C, and IL-10*C/C as well as allelic frequencies of IL-10*T and IL-10*C between patients with major depression and controls in the Korean population. Comparison of genotype and allelic frequencies of IL-10 gene between patients with schizophrenia and controls were also not significant. The present study suggests that IL-10 gene polymorphism at position -819 does not confer susceptibility to major depression and schizophrenia, at least in the Korean population. Further systematic studies including various clinical variables would be required.     

Essential tremor: phenotypes

Classically, essential tremor (ET) was defined by the Movement Disorder Society Consensus Statement on Tremor (1998) as "a bilateral, largely symmetric postural or kinetic tremor involving hands and forearms that is visible and persistent". Additional or isolated tremor of the head may occur but in the absence of abnormal posture. Duration is more than 5 years and the neurological examination is normal, with exception of the cogwheel phenomenon. In the last years ET has evolved into two different meanings. First of all, the classical ET, as a monosymptomatic disorder, and second, a heterogeneous disorder, the Essential Tremors, or a family of diseases. Nowadays, ET can be classified with both motor and non-motor elements. Tremor may occur also in the legs, feet, trunk, jaw, chin, tongue, and voice. Although postural and kinetic tremors are the main features of ET, intentional tremor and tremor at rest may also occur in some patients. Other motor features described in patients with ET are gait ataxia, postural instability and eye-motion abnormalities. Non-motor features include cognitive (memory and executive problems and dementia), psychiatric (anxiety, depression and social phobia), and sensory abnormalities (olfactory deficits, hearing loss).     

A family study of DRD3 rs6280, SLC1A2 rs3794087 and MAPT rs1052553 variants in essential tremor

Background/Objective: Despite many data suggesting a role of genetic factors in the risk for essential tremor (ET), the responsible genes have not been identified. We analyzed in ET Spanish families three single nucleotide polymorphisms (SNPs): DRD3 rs6280, SLC1A2 rs3794087, and MAPT rs1052553) previously related to an increased risk for developing the disease.

Methods: We recruited 45 subjects with ET and 13 subjects without tremor belonging to 11 families who were evaluated because of familial tremor. Diagnosis of probable or definite ET was done according to TRIG criteria. Genotyping of the 3 SNPs was done using TaqMan-based qPCR assays. Data were compared with those of healthy controls of our laboratory. Family-based association testing for disease traits was performed as well.

Results: rs6280 and rs3794087 genotype and allelic frequencies did not differ significantly between subjects with ET and healthy controls. However, rs1052553AA genotype and the allele rs1052553A allele were significantly more frequent among ET patients. rs1052553A allele was non-significantly overrepresented in ET patients compared with controls when considering only the more severely affected member of each ET family. Family-based association test for disease traits showed lack of association between ET and the three SNPs studied.

Conclusions: Our results showed a lack of association between rs6280 and rs3794087 with the risk for ET, though a marginal increased risk for ET was observed among the rs1052553A allele carriers, which was not confirmed with a family-based association study.     

Impact of the proton pump inhibitors and CYP2C19*2 polymorphism on platelet response to clopidogrel as assessed by four platelet function assays

Background

Previous studies suggested a possible negative interference of proton pump inhibitors (PPIs) on clopidogrel’s antiplatelet effect because of the competitive inhibition of the CYP 2C19 isoenzyme. Moreover, carriers of the loss-of-function allele of CYP2C19 polymorphism (CYP2C19*2) display significantly lower responses to clopidogrel. In this study, we investigated the association between CYP2C19*2 genotype, PPI intake and clopidogrel resistance in patients with coronary artery disease (CAD) and their effect on clinical outcome.

Methods

We recruited 95 patients with CAD receiving chronic clopidogrel therapy in combination with aspirin. Platelet reactivity was simultaneously assessed by INNOVANCE PFA-100 P2Y, ADP-induced light transmission aggregometry (LTA), flow-cytometric vasodilator-stimulated phosphoprotein (VASP)-phosphorylation assay and multiple electrode aggregometry (Multiplate). Cardiovascular outcomes were recorded during 1-year follow-up period.

Results

Only platelet reactivity assessed by measuring platelet phosphorylated-VASP demonstrated a significant higher platelet reactivity in carriers of CYP2C19*2 (p = 0.023). The other methods displayed higher - but not statistically significant - platelet reactivity in patients carrying the CYP2C19*2 variant as compared with non-carriers. Patients on PPIs demonstrated almost similar suppression of platelet reactivity in comparison with those not treated with PPIs by all platelet function assays. In logistic regression analysis none of the platelet function assays measurements were related with clinical outcomes. Similarly neither CYP2C19*2 genetic variant nor PPI treatment were associated with adverse clinical events.

Conclusions

PPI co-administration did not influence clopidogrel’s antiplatelet effect on laboratory testing by all platelet function assays used. On the contrary, patients carrying CYP2C19*2 genotype had significantly higher residual platelet reactivity as estimated by VASP-phosphorylation assay.     

Factor structure of motor signs in essential tremor

Motor signs in essential tremor (ET) are varied. Patients may have limb tremors, including postural, kinetic (e.g. writing, pouring), and rest tremors, head tremor, voice tremor, or chin tremor. Factor analysis allows one to determine whether these signs fall into a smaller number of discrete domains. Such an analysis has not been performed on a group of ET cases. ET cases (n = 168) were recruited from the Neurological Institute of New York and a videotaped examination was performed. A factor analysis was performed on 17 motor items. Four distinct factors emerged, explaining 68.7% of the total variance. These were factor I (action tremor in the dominant arm), factor II (action tremor in the nondominant arm), factor III (tremor at rest) and factor IV (chin tremor, head tremor, and voice tremor). The demonstration of these four factors will be of potential use for pathological and genetic studies as well as interventional studies, as will be discussed.     

Cohort study of prevalence and phenomenology of tremor in dementia with Lewy bodies

To study prevalence, specific patterns and response to treatment of tremor in dementia with Lewy bodies (DLB), in comparison with other tremulous disorders prevalence, qualitative and quantitative features of tremor were studied in an incident cohort of 67 dopaminergic treatment naive DLB, 111 Parkinson’s Disease (PD) and 34 Essential Tremor (ET) patients. Tremulous DLB patients (tDLB) were compared with tremulous PD (tPD) and ET patients and followed for 2 years. Double blind placebo-controlled acute drug challenge with l-Dopa and alcohol was performed in all ET, 24 tDLB and 27 tPD. Effects of dopaminergic chronic treatment in all tDLB and tPD patients and primidone in 8 tDLB were also assessed. Tremor occurred in 44.76 % of DLB patients. The tDLB patients presented a complex pattern of mixed tremors, characterized by rest and postural/action tremor, including walking tremor and standing overflow in 50 % tDLB. Standing tremor with overflow was characteristic of tDLB (p < 0.001). Head tremor was more frequent in tDLB than tPD and ET (p = 0.001). The tDLB tremors were reduced by acute and chronic dopaminergic treatments (p < 0.01) but not by alcohol or primidone. Tremor occurs commonly in DLB patients with a complex mixed tremor pattern which shows a significant response to acute and chronic dopaminergic treatments. Recognizing that there is a clinical category of tremulous DLB may help the differential diagnosis of tremors.     

CYP2C19基因型对丙戊酸及其与苯妥英联合用药时血药浓度影响

目的探讨细胞色素P450 2C19(CYP2C19)基因对丙戊酸(VPA)血药浓度,以及VPA和苯妥英(PHT)联合应用时对其VPA血药浓度的影响.方法应用变性高效液相(DHPLC)技术对CYP2C19两个常见的等位基因突变进行了分析;应用荧光偏振免疫法(FPIA)测定口服抗癫痫药物患者的血药浓度.结果81例癫痫患者中CYP2C19外显子4(*3)和外显子5(*2)位点均为野生型(*1/*1)的发生率为37.0%,CYP2C19*2和CYP2C19*3的等位基因频率分别为31.5%和3.7%.单一应用VPA时,弱代谢患者较正常代谢患者的VPA血药浓度有所升高(P＜0.05).联合应用PHT和VPA可使VPA血药浓度显著降低(P＜0.01),CYP2C19正常代谢患者VPA血药浓度降低尤为明显(P＜0.01);在VPA与PHT联合用药过程中,约半数CYP2C19正常代谢患者VPA血药浓度不能达到治疗血药浓度.结论CYP2C19基因多态性影响VPA的血药浓度变化,在联合应用PHT时对VPA血药浓度的影响尤为明显,从而影响抗癫痫的临床疗效.     

Effects of ventral intermediate nucleus deep brain stimulation across multiple effectors in essential tremor

ObjectiveEssential tremor (ET) prominently affects the upper-limbs during voluntary movements, but can also affect the lower-limbs, head, and chin. Although deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of thalamus improves both clinical ratings and quantitative measures of tremor, no study has quantified effects of DBS on tremor across multiple body parts. Our objective was to quantify therapeutic effects of DBS across multiple body parts in ET.MethodsWe performed quantitative assessment of tremor in ET patients who had DBS for at least one year. We assessed tremor on and off VIM-stimulation using triaxial accelerometers on the upper-limbs, lower-limbs, head and chin during seated and standing tasks.ResultsVIM-DBS significantly reduced tremor, but there was no statistical difference in degree of tremor reduction across the measured effectors. Compared to healthy controls, ET patients treated with DBS showed significantly greater tremor power (4–8 Hz) across all effectors during seated and standing tasks.ConclusionsVIM-DBS reduced tremor in ET patients. There was no significant difference in the degree of tremor reduction across the measured effectors.SignificanceThis study provides new quantitative evidence that VIM-DBS is effective at reducing tremor across multiple parts of the body.     

Gamma-aminobutyric acid (GABA) receptor rho (GABRR) polymorphisms and risk for essential tremor

Some clinical and experimental data suggest a possible role of gamma-aminobutyrate (GABA)-ergic mechanisms in the pathophysiology of essential tremor (ET), such as the improvement of ET with some GABAergic drugs and the development of an experimental model of ET in GABA A receptor alpha-1 knockout mice (postural and kinetic tremor and motor incoordination similar to human ET). To investigate the possible association between the GABA receptor subtype rho1, rho2, and rho3 (GABRR1, GABRR2, and GABRR3) genotypes and allelic variants of the single nucleotide polymorphisms GABRR1-M26V (Met26Val, rs12200969), GABRR1-H27R (His26Arg, rs1186902), GABRR2-T455M (Thr55Met, rs282129), and GABRR3-Y205X (Tyr205X, rs832032), and the risk for ET, we studied the frequency of the previously mentioned GABRR genotypes and allelic variants in 200 patients with ET and 250 healthy controls using TaqMan genotyping. The frequencies of the GABBR1 genotypes and allelic variants of the studied polymorphisms did not differ significantly between patients with ET and controls, and were unrelated with the age at onset of tremor, gender, localization of tremor, and response of tremor to ethanol. These data suggest that the single nucleotide polymorphisms studied in the GABBR genes are not related to the risk for ET.     

The cytochrome 2C19*2 and *3 alleles attenuate response to clopidogrel similarly in East Asian patients undergoing elective percutaneous coronary intervention

Introduction

Carriage of CYP2C19*2 allele is associated with diminished platelet response to clopidogrel. However, the loss-of-function impact of CYP2C19*3 allele on antiplatelet effect of clopidogrel has not been definitely verified. We conducted this study to compare decreased response to clopidogrel according to carriage of CYP2C19*2 vs. *3 allele.

Materials and methods

The study included 190 consecutive Korean patients undergoing elective percutaneous coronary intervention. Light transmittance aggregometry and the VerifyNow P2Y₁₂ assay were used to assess platelet reactivity (PR) at least 12 hours after 300-mg loading of clopidogrel. The cutoff of high on-treatment PR (HPR) was defined as 5 μmol/L ADP-induced PR > 50%. CYP2C19 genotype was analyzed by the SNaPshot method.

Results

Carriers of at least one CYP2C19 variant allele were 115 patients (60.5%), and allelic frequency of CYP2C19*2 and *3 was 30.3% and 6.8%, respectively. PR and the rate of HPR increased proportionally according to the number of CYP2C19 variant allele. Carriage of CYP2C19 variant allele was an only independent predictor of HPR in multivariate analysis. When we compare the effect of allelic carriage, there were no significant differences in platelet measures and the rate of HPR between carriers of CYP2C19*2 and/or *3 allele(s) whether they were intermediate or poor metabolizers.

Conclusion

Carriage of CYP2C19*3 allele is associated with diminished antiplatelet effect of clopidogrel, which may be as potent as the loss-of-function effect of CYP2C19*2 allele.     

Association of graded allele-specific changes in CYP2D6 function with imipramine dose requirement in a large group of depressed patients

The inactivation and clearance of the tricyclic antidepressant imipramine is dependent on CYP2D6 activity. First, CYP2C19 converts imipramine into the active metabolite desipramine, which is then inactivated by CYP2D6. This retrospective single center study aimed to prove whether CYP2C19 and ample CYP2D6 genotyping (taking into consideration four null alleles and three decreased-activity alleles) could be used to predict imipramine and desipramine plasma concentrations in depressed patients, and whether genotype-based drug dose recommendations might assist in the early management of imipramine pharmacotherapy. In 181 subjects with major depressive disorder, drug doses were recorded, imipramine and desipramine plasma concentrations were monitored and CYP2C19 (*2) and CYP2D6 genotype (*3, *4, *5, *6, *9, *10, *41 and gene duplication) were obtained, yielding graded allele-specific CYP2D6 patient groups. Desipramine and imipramine+desipramine plasma concentration per drug dose unit, imipramine dose at steady state, and imipramine dose requirement significantly depended on CYP2D6 genotype (Kruskal-Wallis test, P<0.0001). Mean (+/-s.d.) drug dose requirements were 131 (+/-109), 155 (+/-70), 217 (+/-95), 245 (+/-125), 326 (+/-213), and 509 (+/-292) mg imipramine/day in carriers of 0, 0.5, 1, 1.5, 2, and >2 active CYP2D6 genes, respectively. Our protocol for CYP2D6 genotyping will thus importantly aid in the prediction of imipramine metabolism, allowing for the use of an adjusted starting dose and faster achievement of predefined imipramine+desipramine plasma levels in all genetic patient subgroups. Therefore, therapeutic efficacy and efficiency may be improved, the number of adverse drug reactions decreased, and hospital stay reduced.     

Genetic determinants of high on-treatment platelet reactivity in clopidogrel treated Chinese patients

Introduction

Cytochrome P450 (CYP), ATP-binding cassette transporters (ABCB1), and paraoxonase-1 (PON1) play crucial roles in clopidogel absorption and bioactivation. Genetic polymorphisms in these genes have been associated with the variability of the response to clopidogrel, however their contribution to high on-treatment platelet reactivity (HPR) in clopidogrel treated Chinese patients is less known.

Materials and methods

Five-hundred Chinese-Han patients treated with clopidogrel for acute coronary syndrome (ACS) were consecutively recruited from the Department of Geriatric Cardiology, General Hospital of Chinese People’s Liberation Army, from September 2010 to September 2012. We assessed the relations of CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893), CYP2C19*17 (rs12248560), PON1Q129R (rs662) and ABCB1C3435T (rs1045642) to the platelet aggregation after 5 days maintenance dose of clopidogrel administration, and the risk for HPR. The cutoff of HPR was defined as 20 μmol/L adenosine diphosphate (ADP)-induced platelet aggregation > 50%.

Results

Both CYP2C19*2 and *3 alleles were significantly associated with higher platelet aggregation after 5 days maintenance dose of clopidogrel administration (P < 0.00001and P = 0.042, respectively). The platelet aggregation in carriers of at least one CYP2C19 loss-of-function allele (*2 or *3, accounted for 58% of the study population) was obviously higher than that in non-carriers (P < 0.00001). Patients with the CYP2C19*2 allele had a higher risk of HPR than those with the CYP2C19 wild-type genotype [adjusted hazard ratio (HR), 1.56; 95% confidence interval(CI), 1.04–2.33, P = 0.03]. The carriers of at least one CYP2C19 loss-of-function allele could also predict significantly greater risk of HPR compared with non-carriers (adjusted HR1.79,95% CI: 1.33–2.4,P = 0.003). However, the carriage of CYP2C19*3 alone could not predict the risk of HPR significantly (adjusted HR, 1.5; 95% CI: 0.83–3, P = 0.16). Significant relation of CYP2C19*17, PON1Q129R and ABCB1C3435T to the platelet aggregation was not found.

Conclusion

In clopidogrel treated Chinese patients with ACS, carriers of at least one CYP2C19 loss-of-function allele could predict greater risk of HPR, with the impact mainly attributing to CYP2C19*2. Neither ABCB1 nor PON1 genotype could influence the antiplatelet response of clopidogrel in the cohort of Chinese patients.