Iwona Żak

CYP3A5∗3 and C3435T MDR1 Polymorphisms in Prognostication of Drug-Resistant Epilepsy in Children and Adolescents

Drug-resistant epilepsies still remain one of the most profound problems of contemporary epileptology. Several mechanisms of drug resistance are possible; among them, genetic factors have a prominent place. Much importance is attached to genes, which encode enzymes that metabolize antiepileptic drugs CYP 3A, which belong to the family of cytochromes P450 and the genome of multidrug resistance, such as multidrug resistance 1 (MDR1) that expresses P-glycoprotein (P-gp), a drug transporter protein. The aim of the study was to assess the relation between polymorphism of gene CYP3A5 and polymorphism C3435T of MDR1 gene with the occurrence of focal, drug-resistant epilepsy in children and youths up to 18 years of age. The study comprised 85 patients, and their age range was from 33 months to 18 years of age, suffering from epilepsy, partly responding well to treatment, partly drug resistant. The polymorphism of both genes has been analysed using the PCR-RFLP method. The study failed to corroborate association between polymorphism CYP3A5∗3 and C3435T polymorphism in MDR1 gene and pharmacoresistant epilepsy. The results of our research do not confirm the prognostic value of the polymorphisms examined in the prognostication of drug resistance in epilepsies.

APOE Gene ε Polymorphism Does Not Determine Predisposition to Ischemic Stroke in Children

Ischemic stroke in children is relatively rare, but it remains an important medical problem. Previous studies on Polish children have implicated dyslipidemias as significant risk factors in stroke. To search for genetic factors associated with the disease, the possible association between apolipoprotein E gene epsilon polymorphism and childhood stroke was evaluated. The study population consisted of 243 individuals: 72 children with ischemic stroke and 100 of their biological parents and 71 children without any symptoms of stroke. The apolipoprotein E gene epsilon polymorphism was genotyped using restriction fragment length polymorphism methodology. To analyze the possible association between this polymorphism and stroke, the transmission disequilibrium test and the case-control model were used. No preferential distribution of any allele from parents to the affected children was observed. There were also no significant differences in genotype and allele distribution between patients and control subjects. Study findings did not confirm that epsilon polymorphism of the apolipoprotein E gene is a risk factor of ischemic stroke in children.

The C242T polymorphism of the gene encoding cytochrome b-245 alpha is not associated with paediatric ischaemic stroke: family-based and case-control study.

BACKGROUND AND PURPOSE Reactive oxygen species play an important role in the physiology and pathology of cerebral arteries, including ischaemic stroke. The cytochrome b-245 alpha gene (CYBA) encodes cytochrome b-245 alpha light chain (p22phox peptide), a critical element of NAD(P)H oxidases, the most important source of superoxide anion in the cerebral arteries. To search for genetic factors associated with paediatric ischaemic stroke, the possible association between CYBA gene C242T polymorphism and the disease was evaluated. MATERIAL AND METHODS The study group consisted of 238 individuals: children with ischaemic stroke (n = 70), their biological parents (n = 118) and children without any symptoms of stroke (n = 50). The C242T polymorphism was genotyped using polymerase chain reaction - restriction fragment length methodology. To evaluate the possible association between polymorphism and stroke, the transmission disequilibrium test and the case-control method were applied. RESULTS The C242 allele was transmitted more frequently than 242T (62.2% vs. 37.8%) but observed frequencies did not differ significantly from expected (p = 0.10). There were also no significant differences in allele and genotype distribution between patients and control subjects (patients: CC - 50.0%, CT - 38.6%, TT - 11.4% vs. controls: CC - 52.0%, CT - 36.0%, TT - 12.0%). CONCLUSIONS The study did not show that the C242T polymorphism of the CYBA gene is a risk factor of ischaemic stroke in children.

Methylenetetrahydrofolate reductase gene A1298C polymorphism in pediatric stroke--case-control and family-based study.

Moderate hyperhomocysteinemia is one of the risk factors of pediatric stroke. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme, which regulates homocysteine metabolism, and some polymorphisms of gene encoding this enzyme are associated with a decreased activity of the enzyme. The aim of the study was to assess an association between the A1298C polymorphism and pediatric stroke. We also evaluated a possible synergistic effect of A1298C and C677T polymorphisms of this gene. The study group consisted of 88 children after ischemic stroke, 142 of their parents and 111 controls. The A1298C polymorphism was genotyped using the restriction fragment length polymorphism method. We used 2 study designs: a case-control model and a family-based association test. The Statistica 7.1 and EpiInfo 6 softwares were used in all analyses. We did not observe any statistically significant differences either in the transmission of the A allele in the family-based test or in the frequency of the A allele in the patients group compared with the controls. We also did not notice any significant additive or synergistic effects between the A1298C and C677T polymorphisms. An analysis of the results obtained in this study and a critical review of previously published studies indicate that the A1298C polymorphism of the MTHFR gene is not related to ischemic stroke in children.

Relationship between rs854560 PON1 Gene Polymorphism and Tobacco Smoking with Coronary Artery Disease

Paraoxonase-1 (PON1) is the antioxidant marker of high-density lipoproteins protecting against atherosclerosis and coronary artery disease (CAD) phenotype. The purpose of the present study was to determine whether the PON1 gene rs854560 polymorphism (163T>A) is associated with CAD in Polish population. rs854560 was genotyped in 494 subjects: 248 patients with premature CAD and 246 blood donors as a control. We found that the risk of CAD was significantly higher in TT homozygotes than in A allele carriers (OR = 1.87, p = 0.041). The synergistic effect between the TT genotype and cigarette smoking was observed (SIM = 9.81; SI = 14.70). The relative increase in risk from interaction between factors was over 37 (RERI = 36.13). The PON1 polymorphism did not modulate the risk of CAD in response to exposure to other traditional risk factors. In conclusion, the rs854560 polymorphism may modulate the risk of CAD in response to cigarette smoking in Polish population. Carriers of TT genotype seem to be particularly at risk of CAD, when exposed to cigarette smoking.

Relationship between CETP gene polymorphisms with coronary artery disease in Polish population

The cholesteryl ester transfer protein (CETP) gene encodes a hydrophobic glycoprotein that plays a crucial role in the reverse transport of cholesterol. The aim of the present study was to determine whether CETP polymorphisms (rs1532624, rs247616 and rs708272) are associated with coronary artery disease (CAD) in a Polish population. Serum lipid levels and single nucleotide polymorphisms of CETP genes were determined in 494 subjects: 248 patients with premature CAD and 246 blood donors as controls. Selected polymorphisms were examined using TaqMan PCR analysis. We found that CAD risk was significantly higher for CC homozygotes and C allele carriers of the rs247616 polymorphism than for carriers with the T allele (OR 1.89, 95% CI 1.29–2.76, p = 0.001 and OR 1.51, 95% CI 1.14–1.99, p = 0.003) and likewise for the CC genotype of the rs1532624 polymorphism than for those with the A allele (OR 1.59, 95% CI 1.05–2.40, p = 0.026). Moreover, T allele carriers of the rs708272 polymorphism had significantly higher total cholesterol levels compared to CC homozygotes (p < 0.05) in the healthy controls. We also observed an allelic pattern, C(rs2477616)C(rs708272)C(rs1532624), which increased susceptibility to CAD by 43% (OR = 1.43, 95% CI 1.10–1.85, p = 0.006). In conclusion, the rs247616 and rs1532624 polymorphisms of CETP may modulate the risk of CAD in Polish population.

Neonatal arterial ischemic stroke and limb ischemia — clinical course and risk factors analysis

Ilona Kopyta1, Iwona Maruniak-Chudek2, Anna Balcerzyk3, Iwona Żak3, Zbigniew Olczak4, Patrycja Sodowska5 1Department of Paediatrics and Developmental Age Neurology, Chair of Paediatrics, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland 2Department of Intensive Care and Neonatal Pathology, Chair of Paediatrics, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland 3Department of Biochemistry and Medical Genetics, School of Health Sciences in Katowice, Medical University of Silesia, Katowice,Poland 4Division of Diagnostic Imaging and Interventional Radiology, Upper Silesian Child’s Health Center, Katowice, Poland 5Department of Gyneacology and Obstetrics, Chair of Women’s Health, School of Health Sciences in Katowice, Medical University of Silesia, Katowice, Poland