54 research outputs found
The impact of Apolipoprotein E alleles on cognitive performance in patients with Parkinson's disease
Apolipoprotein E (ApoE) is a vital component of several lipoproteins and plays a major role in lipid metabolism. APOE gene comprises of three alleles determined by two single nucleotide polymorphisms (rs429358 and rs7412) resulting in the protein isoforms, among which ApoE4 is a confirmed risk factor for Alzheimer's Disease. However, the impact of APOE genotypes on Parkinson's Disease Dementia (PDD) is still inconclusive. The PDD diagnostic criteria are very inconsistent, and could be complemented with genetic factors. Our study covers a total of 237 patients diagnosed with Parkinson's Disease (PD) according to UK PD Brain Bank criteria, who were classified as subjects with (PDD, n equals 73) and without (nPDD, n equals 164) dementia, using neuropsychological assessment tests. TaqMan real-time PCR assays were used to determine APOE allele. No statistically significant differences in APOE alleles frequencies between nPDD and PDD patients have been observed. The study results revealed that the APOE polymorphism is not associated with cognitive status in PD patients
Effects of common functional MMP12 gene polymorphisms on PD in a Polish population
The present study investigated associations of two functional MMP12 polymorphisms with PD risk and cognitive impairment in PD. A total of 478 study subjects (241 PD and 237 age and sex matched controls) were included in the study. UPDRS score, Hoehn–Yahr staging and Schwab–England scale were used to assess motor abilities and activity during daily life. All patients were classified into groups with dementia (PDD, n=72) and without dementia (nPDD, n=159) based on the neuropsychological assessment. The two most common functional single nucleotide polymorphisms (SNPs) in MMP12 gene were determined using TaqMan real-time PCR assays. Frequencies of evaluated MMP12 rs2276109 alleles and genotypes were similar in PD and the controls, whereas rs652438G allele genotypes were significantly more frequent among healthy individuals (p=0.013, OR 0.47 (0.26–0.85). The rs2276109 and rs652438 allele and genotype frequencies were not associated with dementia in PD patients.
The current results suggest that MMP12 rs652438 but not MMP12 rs2276109 may affect the risk for PD, as the minor G allele genotypes might be a protective factor
Polimorfizm genu oksydoreduktazy cytochromu P450 a farmakokinetyka pantoprazolu u zdrowych ochotników
Genetycznie uwarunkowana aktywność enzymów metabolizujących
leki może mieć znaczenie dla bezpieczeństwa i skuteczności
leczenia. We wcześniejszych badaniach wykazano,
że na aktywność enzymatyczną CYP2C19 może wpływać nie
tylko polimorfizm genu kodującego ten cytochrom, lecz także
zawartość reduktazy cytochromu P450 (POR) w mikrosomach
ludzkich hepatocytów. Ludzki gen POR wykazuje dużą zmienność,
a allel POR*28 jest związany ze zwiększoną aktywnością
reduktazy, co w konsekwencji może prowadzić do zwiększonej
aktywności układu CYP P450, w tym enzymu CYP2C19.
Celem badania było określenie związku pomiędzy polimorfizmem
genu POR a parametrami farmakokinetycznymi pantoprazolu,
substratu CYP2C19 w grupie zdrowych ochotników.
W analizie uwzględniono także warianty genu CYP2C19. U 30 osób, u których wykonano badanie
pod kątem występowania jednonukleotydowych
polimorfizmów:
rs4244285 (681G>A, CYP2C19*2), rs12248560 (-806C>T, CYP2C19*17)
oraz rs1057868 (31696C>T, POR*28). Stężenia pantoprazolu w osoczu
zmierzono metodą wysokosprawnej chromatografii cieczowej
w ciągu 8 godz. od przyjęcia pojedynczej doustnej dawki
leku (40 mg). Nie stwierdzono istotnych różnic w stężeniu pantoprazolu
pomiędzy osobami o różnych genotypach POR (*1/*1,
*1/*28 i *28/*28). Analiza wieloczynnikowa wykazała, że genotyp
CYP2C19 istotnie wpływał na wartość wszystkich analizowanych
parametrów farmakokinetycznych (p < 0.05), podczas
gdy genotyp POR nie był istotnie związany z żadnym z nich. Wyniki badania wskazują, że polimorfizm genu POR
nie wpływa istotnie na farmakokinetykę pantoprazolu.It has recently been demonstrated that CYP2C19
activity may be influenced not only by CYP2C19 polymorphism,
but also cytochrome P450 oxidoreductase (POR) protein abundance
in human liver microsomes. The human POR gene is highly
polymorphic and a common POR*28 allele is associated with
increased POR activity, which may result in increased CYP P450
activity (including CYP2C19).
The aim of the current study was to evaluate the association
between POR and CYP2C19 polymorphisms and CYP2C19 substrate
pharmacokinetics, i.e. pantoprazole, in Polish Caucasian
healthy volunteers. The study enrolled 30 subjects, genotyped
for rs4244285 (681G>A, CYP2C19*2), rs12248560 (-806C>T,
CYP2C19*17) and rs1057868 (31696C>T, POR*28). Pantoprazole
concentration in plasma was determined by validated highperformance
liquid-chromatography method 1 h, 2 h, 3 h, 4 h, 6 h
and 8 h after a single oral 40 mg dose of the drug. No significant differences in the drug concentrations
between POR*1/*1, POR*1/*28 and POR*28/*28 carriers were
observed. Multivariate analysis revealed that the CYP2C19 genotype
significantly influenced all the investigated pharmacokinetic
parameters (p < 0.05), while the POR genotype was not
associated with any of the parameters. The results of the current study suggest that POR
polymorphism does not significantly influence pantoprazole
pharmacokinetics
Risk factors of stroke and −717A>G (rs2794521) CRP gene polymorphism among stroke patients in West Pomerania province of Poland
Background and purpose
Some of the risk factors of ischaemic stroke influence the development of atherosclerosis, which is a significant cause of vascular incidents. An inflammatory component plays a role in pathogenesis of both atherosclerosis and atrial fibrillation, the most important risk factor of embolic strokes. C-reactive protein (CRP) concentration in blood reflects the inflammatory process. Concentration of this protein depends on the CRP gene polymorphism. The aim of the study was to assess the relationship between selected risk factors of stroke and variant of −717A>G (rs2794521) CRP gene polymorphism in population of West Pomerania Province of Poland.
Materials and methods
There were 125 consecutive patients with ischaemic stroke analysed, who met the inclusion and exclusion criteria. In all patients, −717A>G CRP gene polymorphism was genotyped and analysed in relation to selected stroke risk factors.
Results
Prevalence of type 2 diabetes was lower in patients with AA genotype of −717A>G CRP gene polymorphism than in patients with other alleles (p=0.017). Subjects with GG genotype had significantly higher concentration of CRP comparing to AG genotype (p=0.023). No correlation was found between −717A>G CRP gene polymorphism and the lipid profile and other selected risk factors of stroke.
Conclusions
In patients with ischaemic stroke in West Pomerania Province, the GG genotype of −717A>G CRP gene polymorphism is associated with significantly higher CRP concentration in relation to AG genotype. Patients with AA genotype may be characterised by lower prevalence of type 2 diabetes
Effect of the ADRB1 1165C>G and 145A>G polymorphisms on hemodynamic response during dobutamine stress echocardiography
Analysis of common type 2 diabetes mellitus genetic risk factors in new-onset diabetes after transplantation in kidney transplant patients medicated with tacrolimus
CYP2C19 polymorphism affects single-dose pharmacokinetics of oral pantoprazole in healthy volunteers
Lack of association between CAG repeat polymorphism in the androgen receptor gene and the outcome of rheumatoid arthritis treatment with leflunomide
Association study of folate-related enzymes (MTHFR, MTR, MTRR) genetic variants with non-obstructive male infertility in a Polish population
Influence of variation in the catechol-O-methyltransferase gene on the clinical outcome after lumbar spine surgery for one-level symptomatic disc disease: a report on 176 cases
- …