Paweł Niemiec

The 242T variant of the CYBA gene polymorphism increases the risk of coronary artery disease associated with cigarette smoking and hypercholesterolemia.

ObjectivesHypercholesterolemia and cigarette smoking increase superoxide anion production, which is involved in many proatherosclerotic processes. NAD(P)H oxidases are the main source of superoxides in the vasculature, and the phagocyte oxidase (p22phox) encoded by the CYBA gene is a critical component of NAD(P)H oxidases. The 242T CYBA allele is associated with an increased low-density lipoprotein oxidation and superoxide production. This report focuses on the interactions between C242T CYBA polymorphism and traditional risk factors of coronary artery disease (CAD), such as cigarette smoking and hypercholesterolemia. MethodsWe have studied 341 individuals, including 172 patients with angiographically confirmed CAD and 169 blood donors with no known history of cardiovascular disease. The C242T CYBA polymorphism was genotyped using the PCR-restriction fragment-length polymorphism method. To determine the possible interactions between CYBA genotypes and the traditional risk factors for CAD, we used multivariate logistic regression analysis (cumulative effects) and the 4×2 table approach (synergistic/antagonistic effects). ResultsWe have found a strong cumulative effect of the 242T allele carrier state and cigarette smoking and hypercholesterolemia. The risk of CAD associated with the presence of cigarette smoking and hypercholesterolemia was stronger in 242T carriers (odds ratio=17.88, P<0.00000) than in CC homozygotes (odds ratio=3.75, P<0.00000). Estimated CAD risk associated with the presence of the 242T allele and both traditional risk factors was ≈500% greater than the risk predicted by assuming additivity of effects (synergy index, 5.08). ConclusionThe 242T allele interacts with cigarette smoking and hypercholesterolemia to increase the risk of CAD; this risk is probably associated with the cumulative/synergistic effect of the 242T allele and both the traditional risk factors.

Modification of the Coronary Artery Disease Risk Associated with the Presence of Traditional Risk Factors by Insertion/Deletion Polymorphism of the ACE Gene

Cigarette smoking, hypercholesterolemia, and obesity influence the renin-angiotensin system (RAS) functions including an increased synthesis of the angiotensin I converting enzyme (ACE). Thus in the present work we explore the interactions of the ACE gene insertion/deletion (I/D) polymorphism and traditional risk factors. The study cohort included 341 subjects composed of 172 patients with angiographically confirmed CAD and 169 blood donors without a history of cardiovascular diseases. The I/D polymorphism was genotyped using polymerase chain reaction (PCR) methodology. To determine the interactions between the ACE genotypes and traditional risk factors the epidemiologic approach was used (4 x 2 tables and the synergy measures). The frequency of the DD genotype was significantly higher in patients than in controls (33.7% versus 21.3%, odds ratio [OR] = 1.88, 95% CI; 1.13-3.15, p = 0.010), but greater differences were found in males (35.7% versus 20.5%, OR = 2.15, 95% CI: 1.14-4.04, p = 0.010). We found a synergy of the DD genotype with smoking (SI = 1.88, SIM = 1.22), total cholesterol > or =5 mmol/l (SI = 2.12, SIM = 1.31) and elevated low density lipoprotein (LDL) cholesterol level (> or =3 mmol/l) (SI = 1.78, SIM = 1.14). The presence of the D allele (DD + ID subjects) also increased the risk of coronary artery disease (CAD) associated with the presence of elevated total cholesterol and LDL cholesterol (SI = 1.69, SIM = 1.18, in both cases), elevated level (> or =1.7 mmol/l) of triacylglycerols (SI = 1.81, SIM = 1.18) and overweight/obesity (SI = 4.25, SIM = 2.36). In each case the estimated CAD risk was greater than that predicted by assuming the additivity of effects (the risk increased from 69% for the D allele - total cholesterol interaction to 325% for the D allele - overweight/obesity). The statistical significance was also confirmed by a multiplicative model of synergy. The DD genotype/D allele of the ACE gene increases the risk of CAD associated with the presence of traditional risk factors.

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 CYBA gene A640G polymorphism influences predispositions to coronary artery disease through interactions with cigarette smoking and hypercholesterolemia.

The CYBA gene encodes the p22phox peptide, an essential subunit of vascular NADPH oxidases. The aim of the study was to analyze potential interactions between CYBA gene A640G polymorphism and traditional risk factors of atherosclerosis. We studied 320 subjects: 160 patients with coronary artery disease (CAD) and 160 controls. The results of interactions were interpreted on the basis of synergy index values (SI, SIM). The 640G allele interacted with cigarette smoking (SI = 2.02, SIM = 2.32). Even greater increase of the CAD risk was found whenever the 640G allele interacted with both smoking and hypercholesterolemia (SI = 2.70, SIM = 3.60). The results suggest that the A640G polymorphism may influence individual predispositions to CAD through interactions with smoking and hypercholesterolemia.

The D allele of angiotensin I-converting enzyme gene insertion/deletion polymorphism is associated with the severity of atherosclerosis

Abstract Background: Angiotensin II is produced primarily by angiotensin I-converting enzyme (ACE) within atherosclerotic lesions and ACE level in plaques correlates with the severity of vessel wall damage. Therefore, we investigated the possible association of ACE gene insertion/deletion (I/D) polymorphism and the severity of atherosclerosis, estimated on the basis of the number of coronary stenoses and critical arterial occlusions observed during coronary angiography. Methods: The study cohort included 172 patients with angiographically confirmed premature coronary artery disease. The ACE gene I/D polymorphism was genotyped using a PCR method. Results: The frequencies of DD genotype, D allele carrier-state (DD+ID genotypes) and the D allele increased with the number of stenoses in coronary vessels. D allele carriers (DD+ID genotypes) were more frequent in the subgroup of patients with stenoses in at least four coronary vessels than in other patients including subjects with one-, two- and three-vessel disease (97.4% vs. 74.4%, OR=13.05, 95% CI: 1.81–100.00, χ2=9.84, p=0.0017). Furthermore, the D allele was significantly more frequent in patients with critical arterial occlusions (>90%) than in subjects without critical stenoses (61.1% vs. 49.3%, χ2=9.84, p=0.023). Conclusions: The ACE I/D polymorphism influences individual differences in severity of coronary artery disease and the D allele promotes generation of numerous and critical atherosclerotic lesions. Clin Chem Lab Med 2008;46:446–52.

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.

Polymorphisms of genes encoding coagulation factors II, V, VII, and XIII in relation to pediatric ischemic stroke: family-based and case-control study.

Background:The investigation of a possible association between the FII, FV, FVII, and FXIII genes polymorphisms and pediatric ischemic stroke (IS). Methods:The study group consisted of 392 individuals, including 81 children with IS, their biological parents (n=162), and 149 control children. The polymorphisms were genotyped using polymerase chain reaction-restriction fragments length polymorphism method. The relation between analyzed polymorphisms and the disease was tested by 2 independent methods: family-based association test—transmission/disequilibrium test (TDT) and classic case-control model. Results:We did not observe any preferential distribution of any analyzed allele from parents to the affected children. For the FVII gene polymorphism, there was a trend toward a higher frequency of the R allele. In a case-control model, the differences between the patients and controls in the frequency of the Q allele, Q allele carriers, and RR homozygotes lay close to the border of statistical significance (P=0.08). There were no significant differences in genotype and allele distribution between patients and controls in case of other polymorphisms. Conclusions:Analyzed polymorphisms of coagulation factors are not significant determinants of pediatric IS in the studied population; however, these findings require a confirmation in a larger group of participants.

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.

Five-year prevalence of recurrent shoulder dislocation in the entire Polish population

PurposeThe aim of this study was to evaluate five-year prevalence of recurrent shoulder dislocation in the entire Polish population.MethodsThe study involved the entire Polish population between 01 January 2010 and 31 December 2014. Demographic data were retrieved from the Central Statistical Office of Poland. Data on the number of shoulder joint dislocations were retrieved from the database of the National Health Fund.ResultsWe identified 32,253 Polish residents with shoulder instability. About 0.1% of Polish residents suffered from recurrent shoulder dislocation. Males suffered almost two times more often than females (66% and 34%, respectively), and male gender was recognized as a risk factor of instability (OR = 2.07, p <10–10). Females in their eighth decade of life had the highest risk of recurrent shoulder dislocation (OR = 3.33, p <10–10). In males the highest risk of recurrences was noted for the third decade of life (OR = 1.78, p <10–10).ConclusionThe period prevalence rate of recurrent shoulder dislocation in Poland is 83.7 per 100,000 persons per five years. The rate of recurrent shoulder dislocation for the general Polish population is 0.1%. Males suffered from recurrent shoulder dislocation almost twice as frequently as females (OR = 2.07).