Malnutrition Risk in Kidney Recipients Treated With Mycophenolate Mofetil Is Associated With IMPDH1 rs2278294 Polymorphism

Background

Malnutrition is known to increase morbidity and mortality in renal transplant recipients, whereas little is known about genetic predisposition to low body mass index (BMI) in the transplant setting. Inosine monophosphate dehydrogenase (IMPDH) regulates intracellular fat accumulation, pre-adipicytes maturation, and is a target of mycophenolic acid (MPA) used as a standard immunosuppressant. We hypothesized that MPA may interfere with fat tissue formation and weight gain in kidney transplant recipients and this process may be modified by IMPDH1 or IMPDH2 (genes encoding constitutive and inducible IMPDH) small nucleotide polymorphism variants.

C3435T polymorphism of the ABCB1/MDR1 gene encoding P-glycoprotein in patients with inflammatory bowel disease in a Polish population

BackgroundInflammatory bowel disease (IBD) belongs to the group of chronic diseases of the gastrointestinal tract, prevalence of which is increasing in the Polish population. The two main clinical types of IBD are ulcerative colitis (UC) and Crohn’s disease (CD). The expression level of the ABCB1/MDR1 gene which encodes P-glycoprotein seems to be of great prognostic relevance while evaluating patients’ susceptibility to UC or CD. One of the most significant ABCB1/MDR1 gene mutations is the C3435T polymorphism. A decreased expression of the ABCB1/MDR1 gene and lower P-glycoprotein activity has been associated with the 3435T variant. The aim of the study was to evaluate the C3435T polymorphism in the IBD patients and to investigate a possible correlation with disease susceptibility.MethodsThe study was performed on 108 patients with IBD and on 137 healthy individuals. All the participants were of Caucasian origin and came from central Poland. The C3435T polymorphism was analyzed by using the PCR-RFLP method.ResultsOur results showed that ORs for IBD development (including UC and CD) were elevated in individuals both with the 3435CC genotype and the 3435C allele. The differences in genotype and allele frequencies were not significant.ConclusionsThe C3435T polymorphism of the ABCB1/MDR1 gene is not a risk factor for IBD, including UC and CD, in the population coming from central Poland.     

The multidrug transporter P-glycoprotein in pharmacoresistance to antiepileptic drugs

This review provides an overview of the knowledge on P-glycoprotein (P-gp) and its role as a membrane transporter in drug resistance in epilepsy and drug interactions. Overexpression of P-gp, encoded by the ABCB1 gene, is involved in resistance to antiepileptic drugs (AEDs), limits gastrointestinal absorption and brain access of AEDs. Although several association studies on ABCB1 gene with drug disposition and disease susceptibility are completed to date, the data remain unclear and incongruous. Although the literature describes other multidrug resistance transporters, P-gp is the main extensively studied drug efflux transporter in epilepsy.     

Expression of genes involved in xenobiotic metabolism and transport in end-stage liver disease: up-regulation of ABCC4 and CYP1B1

BackgroundExpression of drug-metabolizing enzymes and drug transporters in liver is mainly regulated by a system of nuclear receptors. The aim of the current study was to investigate the expression of nuclear receptors, as well as these enzymes and transporters, in liver samples from patients suffering from end-stage liver disease of various etiologies (HCV infection, alcohol liver disease, and primary sclerosis cholangitis).MethodsGene expression was measured using quantitative real-time PCR with surgical specimens from livers of patients with end-stage liver disease, and non-tumoral liver tissue that served as control.ResultsOur study confirmed that the expression of most phase I enzymes is suppressed in end-stage liver disease, and is correlated with a decrease in NR1I2 and NR1I3, the main regulators of xenobiotic metabolism. While mRNA levels of phase II enzymes were generally unchanged, some ABC transporters were up-regulated. The most spectacular increases in expression were observed with ABCC4 (MRP4) – at the mRNA level, and CYP1B1 – at both the mRNA and protein levels. We also demonstrated that IL-6 can induce CYP1B1 expression independently of CYP1A1, in a human hepatocellular liver carcinoma cell line.ConclusionsAs CYP1B1 is an enzyme which converts various substrates into carcinogenous metabolites, its overexpression in liver may be one of the factors increasing the risk of hepatic cancers inpatients with liver disease. CYP1A1 and CYP1B1 are often referred to as model AHR target genes, but CYP1A1 was down-regulated in diseased liver samples. This points to the existence of differences in regulation of these two genes.     

Event-related desynchronization of sensorimotor EEG rhythms in hemiparetic patients with acute stroke

Previous neuroimaging studies based on neurovascular coupling have shown that stroke affects both, strength and spatial extent of brain activation during upper limb movements. Here, we investigated the sub-second amplitude dynamics of a direct neuronal measure, i.e., event-related desynchronization (ERD) of EEG oscillations during finger movements, in patients with acute cortical and subcortical stroke. Acute cortical strokes were found to decrease the ERD of alpha oscillations for the affected pericentral sensorimotor areas compared to a control group. Within the cortical stroke group, the affected hemisphere showed a smaller alpha-ERD compared to the unaffected hemisphere when each was contralateral to the acting hand. Furthermore, when cortical stroke patients moved their paretic hand, the ipsilateral (i.e., contralesional) alpha-ERD was stronger than the contralateral (ipsilesional) ERD. Interestingly, the alpha-ERD amplitude in a hemisphere with a cortical stroke was relatively well preserved for non-paretic hand movements compared to alpha-ERD amplitude for paretic hand movements. This finding provides a new perspective for assessing the rehabilitative potential, which could be utilized through training of the still responsive cortical network, e.g., via enforced use of the paretic hand.     

Genetic polymorphisms of CYP2D6 oxidation in patients with systemic sclerosis

Background  

Involvement of genetic and environmental factors in the pathogenesis of scleroderma has contributed to a number of studies whose aim is to elucidate the way in which xenobiotics exert effects on the occurrence of autoimmune processes resulting in development of systemic sclerosis (SSc).