Ischemic stroke commonly affects older individuals in China and worldwide. Such events are caused by a blood clot that blocks a vessel supplying blood to the brain. However, the etiology and pathogenesis of ischemic stroke are not fully understood. Genetics may play an important role in these events; indeed, rapid progress through the Human Genome Project has allowed the localisation and identification of genes related to ischemic stroke (1). Some single-gene disorders such as Fabry disease and sickle cell disease include ischemic stroke as a feature of the disorder, while in other cases, genetic variants appear to increase individual susceptibility to ischemic events.Polymorphisms in the members of the integrin family of genes, specifically integrin alpha-2 (ITGA2) and integrin beta-3 (ITGB3), are associated with thrombotic and arterial atherosclerotic disease (2, 3). Integrins are adhesion molecules that promote platelet aggregation, contributing to the development of blood clots (4). This function makes them intriguing candidates for the pathogenesis of ischemic stroke. Several polymorphisms have been identified in ITGA2 and ITGB3, but two, a C807T polymorphism (rs1126643 in ITGA2) and a T176C polymorphism (rs5918 in ITGB3), are associated with myocardial infarction and cerebral infarction (5, 6). Reiner et al. (7) found that ITGA2 C807T polymorphism was correlated with cerebral stroke in young women, and thus proposed that the T allele might be a hereditary susceptibility allele predisposing young women t o cerebral stroke. Similarly, Maakaroun et al. (8) found, through investigation on the ITGA2 C807T polymorphism in young twins, that the 807T allele was more frequent in twins with stroke than in those without stroke. However, Nikolopoulos et al. (5) found no correlation between the ITGA2 C807T polymorphism and incidence of ischemic stroke. Because genetic polymorphisms can differ between races/ethnicities, and few studies have been performed to date on ITGA2 and ITGB3 polymorphisms and ischemic stroke, it remains unclear whether ITGA2 C807T is related to ischemic stroke (9).We hypothesised that polymorphisms in ITGA2 and ITGB3 could increase susceptibility to ischemic stroke in Background: Recent studies have reported contrasting results regarding the association of polymorphisms in two integrin genes, ITGA2 and ITGB3, with ischemic stroke. Aims: The present study aimed to investigate the correlation between the ITGA2 C807T and ITGB3 T176C polymorphic loci with ischemic stroke, as well as plasma lipid and lipoprotein levels. Study Design: Case control study. Methods: Human venous blood samples were collected from patients admitted for ischemic stroke (n=350, 'patients') and healthy individuals (n=300, 'controls'). Blood was genotyped at these loci by polymerase chain reaction-restriction fragment length polymorphism. Plasma lipid and lipoprotein levels were measured by routine enzymatic, masking, and turbidimetry methods. Results:As expected, total cholesterol, triglycerides, and low-density lipoprotein we...

Background This study aimed to investigate the influence of CYP2D6 polymorphisms on risperidone plasma concentrations in patients with schizophrenia. Based on pharmacogenomics, we examined whether plasma concentration of risperidone is associated with clinical response and adverse side-effects. Methods We recruited patients with chronic schizophrenia who were then treated with risperidone. The CYP2D6 genotypes were determined using targeted sequencing. All high-frequency mutation sites of the nine exons of the gene were assayed in the present study. Plasma concentrations of risperidone and 9-hydroxyrisperidone (9-OH-RIS) were measured using high-performance liquid chromatography (HPLC). Psychiatric symptoms were monitored using The Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI). Adverse effects were evaluated using the Barnes Akathisia Scale (BAS) and Extrapyramidal Symptom Rating Scale (ESRS). Follow-up visits were scheduled at weeks 2,4, and 8 after treatment initiation. Results Among the 76 patients, 100 C > T (rs1065852), 1038 C > T (rs1081003), 1662 G > C (rs1058164), 2851 C > T (rs16947), and 4181G > C (rs1135840) variants were detected. The most common allele was CYP2D6*10 (81.6%), whereas CYP2D6*2 (9.2%) and CYP2D6*5 (17.1%) were relatively rare. Plasma levels of risperidone and the risperidone/9-OH risperidone ratio (R/9-OH) were significantly increased in individuals with CYP2D6*10 (P < 0.05). The change in PANSS score, weight, high-density lipoprotein (HDL) level, prolactin (PRL) level, and ESRS were significantly different from baseline, between the different genotypes (P < 0.01). Moreover, individuals with CYP2D6*10 homozygous (TT) mutations were associated with higher risperidone concentration and R/9-OH ratio than those with heterozygous mutations (CT) (P < 0.01). A change from baseline in BPRS scores was observed only during week 8 and was different between heterozygous and homozygous mutations. As for the C2851T polymorphism, the incidence of adverse metabolic effects was significantly different between the C/C and C/T genotypes (P < 0.01). Regarding the G4181C polymorphisms, the changes from baseline in GLU and TG, were different between the C/C and C/G genotypes (P < 0.01). Conclusions The genotype of CYP2D6 significantly influences the plasma concentration of risperidone and may subsequently influence the adverse side-effects following risperidone treatment, while also exerting a slight influence on clinical outcomes.