Association between C677T polymorphism of MTHFR gene and risk of amyotrophic lateral sclerosis: Polish population study and a meta-analysis

Objective Genetic factors play a role in pathogenesis of amyotrophic lateral sclerosis (ALS). A few studies demonstrated that the TT genotype of C677T polymorphism of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene can increase the risk of sporadic ALS. The aim of our study was to determine the relationship between C677T polymorphism of MTHFR gene and the risk of sporadic ALS in Polish population and to perform the meta-analysis assessing the significance this polymorphism for the risk of ALS in Caucasian population. Methods We included 251 patients with ALS and 500 control subjects recruited from Polish population and performed the meta-analysis of published data from Caucasian population. MTHFR C677T polymorphism was genotyped using a TaqMan assay and 7900HT Fast real Time PCR System. Results The frequency of genotypes did not differ significantly between Polish ALS patients and control subjects (CC: 45.0 vs 45.8%, CT: 48.2 vs 45.0%, TT: 6.8 vs 9.2%, P=0.46). The meta-analysis including 863 ALS patients and 1362 controls revealed that TT genotype increases the risk of sporadic ALS in Caucasian population. Conclusion Although we did not find the association between C677T polymorphism of MTHRF gene and risk of ALS in Polish population, the results of meta-analysis suggest that the TT genotype can be a genetic risk factor for ALS in Caucasian population

Polimorfizm –455G/A genu β-fibrynogenu a ryzyko udaru niedokrwiennego w populacji polskiej

Background and purpose: Ischaemic stroke is considered to be multifactorial and interactions between environmental and genetic factors play an important role. Although vascular risk factors are well known, the genetic ones are still undiscover - ed. In the present study, we assessed the significance of the β-fibrinogen –455G/A gene polymorphism and the risk of ischaemic stroke in a Polish population. Material and methods: 426 ischaemic stroke patients classified according to stroke aetiologies (small vessel disease, large vessel disease or cardioembolic stroke) and 234 controls were included in the study. The association of the β-fibrinogen genotypes with ischaemic stroke was tested using logistic regression analysis under dominant, recessive or additive models of inheritance. Results: The allele and genotype distributions of the β-fibri - nogen –455G/A gene polymorphism did not differ significantly between patients and controls (patients: G – 75%, GG – 56.6%, GA – 36.8%, AA – 6.6%; controls: G – 73.7%, GG – 57.3%, GA – 32.9%, AA – 9.8%; p > 0.05, χ2). In addition, logistic regression analysis adjusted for the known risk factors, i.e. hypertension, ischaemic heart disease, myocardial infarction, hypercholesterolaemia, diabetes mellitus and smoking, did not show a role of the studied polymorphism in ischaemic stroke. Conclusions: The β-fibrinogen –455G/A gene polymorphism is not a risk factor for ischaemic stroke in a Polish population

Polimorfizm –455G/A genu β-fibrynogenu a ryzyko udaru niedokrwiennego w populacji polskiej

Background and purpose Ischaemic stroke is considered to be multifactorial and interactions between environmental and genetic factors play an important role. Although vascular risk factors are well known, the genetic ones are still undiscovered. In the present study, we assessed the significance of the β-fibrinogen –455G/A gene polymorphism and the risk of ischaemic stroke in a Polish population. Material and methods 426 ischaemic stroke patients classified according to stroke aetiologies (small vessel disease, large vessel disease or cardioembolic stroke) and 234 controls were included in the study. The association of the β-fibrinogen genotypes with ischaemic stroke was tested using logistic regression analysis under dominant, recessive or additive models of inheritance. Results The allele and genotype distributions of the β-fibrinogen –455G/A gene polymorphism did not differ significantly between patients and controls (patients: G – 75%, GG – 56.6%, GA – 36.8%, AA – 6.6%; controls: G – 73.7%, GG – 57.3%, GA – 32.9%, AA – 9.8%; p > 0.05, χ2). In addition, logistic regression analysis adjusted for the known risk factors, i.e. hypertension, ischaemic heart disease, myocardial infarction, hypercholesterolaemia, diabetes mellitus and smoking, did not show a role of the studied polymorphism in ischaemic stroke. Conclusions The β-fibrinogen –455G/A gene polymorphism is not a risk factor for ischaemic stroke in a Polish population.Wstęp i cel pracy Etiologia udaru niedokrwiennego mózgu jest wieloczynnikowa. Istotną rolę odgrywają w niej interakcje pomiędzy czynnikami środowiskowymi i genetycznymi. Naczyniowe czynniki ryzyka udaru mózgu są dość dobrze poznane, natomiast rola czynników genetycznych pozostaje wciąż niejasna. W prezentowanym badaniu oceniano znaczenie polimorfizmu –455G/A genu β-fibrynogenu w kontekście ryzyka wystąpienia udaru niedokrwiennego mózgu w populacji polskiej. Materiał i metody Do badania włączono 426 chorych na udar niedokrwienny mózgu sklasyfikowanych zgodnie z etiologią udaru (choroba małych naczyń, choroba dużych naczyń lub udar sercowozatorowy) oraz 234 osoby z grupy kontrolnej. Związek pomiędzy badanym polimorfizmem a udarem niedokrwiennym mózgu został zbadany przy użyciu regresji logistycznej w dominującym, recesywnym i addytywnym modelu dziedziczenia. Wyniki Nie stwierdzono istotnej różnicy w rozkładzie alleli i genotypów polimorfizmu –455G/A genu β-fibrynogenu pomiędzy pacjentami a osobami z grupy kontrolnej (pacjenci: G – 75%, GG – 56,6%, GA – 36,8%, AA – 6,6%; grupa kontrolna: G – 73,7%, GG – 57,3%, GA – 32,9%, AA – 9,8 %; p > 0,05, test χ2). Ponadto w modelu regresji logistycznej uwzględniającym wpływ znanych czynników ryzyka, takich jak: nadciśnienie tętnicze, choroba niedokrwienna serca, zawał mięśnia sercowego, hipercholesterolemia, cukrzyca i palenie tytoniu, nie wykazano roli badanego polimorfizmu w udarze niedokrwiennym mózgu. Wnioski Polimorfizm –455G/A genu β-fibrynogenu nie jest czynnikiem ryzyka udaru niedokrwiennego mózgu w populacji polskiej

Association between C677T polymorphism of MTHFR gene and risk of amyotrophic lateral sclerosis : polish population study and a meta-analysis

Objective: Genetic factors play a role in pathogenesis of amyotrophic lateral sclerosis (ALS). A few studies demonstrated that the TT genotype of C677T polymorphism of the 5,10- methylenetetrahydrofolate reductase (MTHFR) gene can increase the risk of sporadic ALS. The aim of our study was to determine the relationship between C677T polymorphism of MTHFR gene and the risk of sporadic ALS in Polish population and to perform the metaanalysis assessing the significance this polymorphism for the risk of ALS in Caucasian population. Methods: We included 251 patients with ALS and 500 control subjects recruited from Polish population and performed the meta-analysis of published data from Caucasian population. MTHFR C677T polymorphism was genotyped using a TaqMan assay and 7900HT Fast real Time PCR System. Results: The frequency of genotypes did not differ significantly between Polish ALS patients and control subjects (CC: 45.0 vs 45.8%, CT: 48.2 vs 45.0%, TT: 6.8 vs 9.2%, P = 0.46). The metaanalysis including 863 ALS patients and 1362 controls revealed that TT genotype increases the risk of sporadic ALS in Caucasian population. Conclusion: Although we did not find the association between C677T polymorphism of MTHRF gene and risk of ALS in Polish population, the results of meta-analysis suggest that the TT genotype can be a genetic risk factor for ALS in Caucasian population

The AGTR1 gene A1166C polymorphism as a risk factor and outcome predictor of primary intracerebral and aneurysmal subarachnoid hemorrhages

Associations between the angiotensin II type 1 receptor (AGTR1) gene A1166C polymorphism and hypertension, aortic abdominal aneurysms (as a risk factor) as well as cardiovascular disorders (as a risk factor and an outcome predictor) have been demonstrated. We aimed to investigate the role of this polymorphism as risk factors and outcome predictors in primary intracerebral hemorrhage (PICH) and aneurysmal subarachnoid hemorrhage (aSAH). We have prospectively recruited 1078 Polish participants to the study: 261 PICH patients, 392 aSAH patients, and 425 unrelated control subjects. The A1166C AGTR1 gene polymorphism was studied using the tetra-primer ARMS-PCR method. Allele and genotype frequencies were compared with other ethnically different populations. The A1166C polymorphism was not associated with the risk of PICH or aSAH. Among the aSAH patients the AA genotype was associated with a good outcome, defined by a Glasgow Outcome Scale of 4 or 5 (p < 0.02). The distribution of A1166C genotypes in our cohort did not differ from other white or other populations of European descent. In conclusion, we found an association between the A1166C AGTR1 polymorphism and outcome of aSAH patients, but not with the risk of PICH or aSAH

The FGA Thr312Ala polymorphism and risk of intracerebral haemorrhage in Polish and Greek populations

Background and purpose Spontaneous intracerebral haemorrhage (ICH) is the most fatal form of stroke with the highest morbidity and disability rate of all stroke types. Recent data suggest that the genetic background has a sizeable and mostly undiscovered effect on the brain haemorrhage risk. Since the coagulation system is crucial to ICH pathology, we studied the significance of the FGA Thr312Ala polymorphism in two European populations. Materials and methods We genotyped 550 and 224 controls as well as 261 and 242 stroke patients in Polish and Greek populations, respectively. The ICH diagnosis was confirmed by computed tomography. The FGA Thr312Ala polymorphism was analysed using real-time polymorphism chain reaction. Results Both crude and multivariable regression analyses showed that the studied polymorphism is a protective factor in the Polish population under the dominant and additive models of inheritance. Those results did not replicate in the Greek population. The meta-analysis of results from the Polish and the Greek populations proved that FGA Thr312Ala polymorphism affects the risk of ICH in the dominant model of inheritance. Conclusions The FGA Thr312Ala polymorphism affects a risk for ICH in the Polish but not in the Greek population. An advanced meta-analysis of well-designed studies with a significant number of cases might provide useful information of novel polymorphisms, including the FGA Thr312Ala polymorphism, and their role in ICH pathology

Polimorfizm –A162G genu PON1 jako czynnik ryzyka rozwoju sporadycznej postaci stwardnienia bocznego zanikowego

Background and purpose Sporadic amyotrophic lateral sclerosis (sALS) is a devastating neurodegenerative disease, which results from complex genetic and environmental interactions. Recent studies have reported an association between several polymorphisms of the PON1 and PON2 genes and risk of sALS. The aim of the present study was to identify an association between the – A162G polymorphism of the promoter region of the human PON1 gene and the risk of sALS in a Polish population. Material and methods We included 259 patients with a diagnosis of definite or probable sALS (76 bulbar onset, 183 limb onset) and 694 healthy controls matched for age and sex. The diagnosis of ALS was established according to El Escorial criteria. The polymorphism was studied by Single Nucleotide Polymorphism Real-Time Polymerase Chain Reaction analysis. Results No overall difference in the PONI – A162G genotype and allele distribution was seen between cases and controls (all p &gt; 0.05). There was, however, a difference in the A allele frequency when the bulbar onset group was compared to the controls (p = 0.03), but this significance disappeared after the Bonferroni correction. Conclusions The results did not show that the – A162G polymorphism of the PON1 gene is a risk factor of sALS in a Polish population; it may affect, however, bulbar onset of the disease.Wstęp i cel pracy Sporadyczna postać stwardnienia bocznego zanikowego (sSLA) jest chorobą zwyrodnieniową układu nerwowego, w której etiopatogenezie kluczową rolę odgrywają interakcje między czynnikami genetycznymi i środowiskowymi. Dotychczasowe badania wskazują na istnienie zależności między polimorfizmami genów PON1 i PON2 a ryzykiem wystąpienia sSLA. Celem pracy było zbadanie, czy istnieje związek między polimorfizmem – A162G miejsca promotorowego genu PON1 a ryzykiem wystąpienia sSLA w populacji polskiej. Materiał i metody Badanie przeprowadzono u 259 chorych, uktórych zgodnie z kryteriami El Escorial rozpoznano pewne lub prawdopodobne SLA (76 osób z postacią opuszkową, 183 osoby z postacią kończynową) oraz u 694 zdrowych ochotników, stanowiących grupę kontrolną dobraną pod względem wieku i płci. Polimorfizm genu PON1 był badany za pomocą reakcji łańcuchowej polimerazy DNA z analizą ilości produktu w czasie rzeczywistym. Wyniki Nie stwierdzono istotnych statystycznie różnic w rozkładzie genotypów i alleli genu PON1 między grupą chorych a grupą kontrolną (p &gt; 0,05). Stwierdzono natomiast różnice w częstości występowania allela A między grupą chorych z postacią opuszkową w porównaniu z grupą kontrolną (p = 0,03), jednak po korekcie Bonferroniego wynik ten nie był już istotny statystycznie. Wnioski Wyniki naszego badania nie wykazały, aby polimorfizm – A162G genu PON1 był czynnikiem ryzyka sSLA w populacji polskiej, jednak sugerują, że może mieć znaczenie dla wystąpienia postaci opuszkowej tej choroby

The AGTR1 gene A1166C polymorphism as a risk factor and outcome predictor of primary intracerebral and aneurysmal subarachnoid hemorrhages

Associations between the angiotensin II type 1 receptor (AGTR1) gene A1166C polymorphism and hypertension, aortic abdominal aneurysms (as a risk factor) as well as cardiovascular disorders (as a risk factor and an outcome predictor) have been demonstrated. We aimed to investigate the role of this polymorphism as risk factors and outcome predictors in primary intracerebral hemorrhage (PICH) and aneurysmal subarachnoid hemorrhage (aSAH). We have prospectively recruited 1078 Polish participants to the study: 261 PICH patients, 392 aSAH patients, and 425 unrelated control subjects. The A1166C AGTR1 gene polymorphism was studied using the tetra-primer ARMS-PCR method. Allele and genotype frequencies were compared with other ethnically different populations. The A1166C polymorphism was not associated with the risk of PICH or aSAH. Among the aSAH patients the AA genotype was associated with a good outcome, defined by a Glasgow Outcome Scale of 4 or 5 (p&lt;0.02). The distribution of A1166C genotypes in our cohort did not differ from other white or other populations of European descent. In conclusion, we found an association between the A1166C AGTR1 polymorphism and outcome of aSAH patients, but not with the risk of PICH or aSAH

Methodological challenges and biases in the field of cognitive function among patients with chronic kidney disease

Chronic kidney disease (CKD) affects approximately 850 million people globally and is associated with an increased risk of cognitive impairment. The prevalence of cognitive impairment among CKD patients ranges from 30 to 60%, and the link between CKD and cognitive impairment is partially understood. Methodological challenges and biases in studying cognitive function in CKD patients need to be addressed to improve diagnosis, treatment, and management of cognitive impairment in this population. Here, we review the methodological challenges and study design issues, including observational studies’ limitations, internal validity, and different types of bias that can impact the validity of research findings. Understanding the unique challenges and biases associated with studying cognitive function in CKD patients can help to identify potential sources of error and improve the quality of future research, leading to more accurate diagnoses and better treatment plans for CKD patients.</p

Cognitive disorders in patients with chronic kidney disease:Approaches to prevention and treatment

Background: Cognitive impairment is common in patients with chronic kidney disease (CKD), and early intervention may prevent the progression of this condition. Methods: Here, we review interventions for the complications of CKD (anemia, secondary hyperparathyroidism, metabolic acidosis, harmful effects of dialysis, the accumulation of uremic toxins) and for prevention of vascular events, interventions that may potentially be protective against cognitive impairment. Furthermore, we discuss nonpharmacological and pharmacological methods to prevent cognitive impairment and/or minimize the latter's impact on CKD patients' daily lives. Results: A particular attention on kidney function assessment is suggested during work-up for cognitive impairment. Different approaches are promising to reduce cognitive burden in patients with CKD but the availabe dedicated data are scarce. Conclusions: There is a need for studies assessing the effect of interventions on the cognitive function of patients with CKD.</p