Objective The aim of the study was to evaluate the association of individual and combined single‐nucleotide polymorphisms in brain‐derived neurotrophic factor (BDNF), dopamine transporter (DAT), and catechol‐O‐methyltransferase (COMT) genes with the occurrence of motor levodopa‐induced complications (MLIC) in Parkinson's disease (PD). Materials and Methods We studied 76 patients with PD (MLIC occurred in 56.6%) and 60 controls. Allelic discrimination of rs6265 BDNF (Val66Met), rs397595 DAT (SLC6A3), and rs4680 COMT (Val158Met) genes were genotyped. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using multinominal logistic regression. Orthogonal partial least squares (OPLS) analysis and OPLS discriminant analysis (OPLS‐DA) were used to analyze qualitative genetic data. Results The risk of PD in subjects with the AG BDNF genotype was increased sixfold (OR = 6.12, 95% CI = 2.88–13.02, p < .0001), and AG BDNF and AG DAT genotypes were correlated with PD in OPLS‐DA (VIP > 1). There were no differences in distributions of BDNF, DAT and COMT genotypes between PD groups with and without MLIC, while OPLS model showed that genotype combination of AG BDNF, AG DAT, and GG COMT was correlated with MLIC and genotypes combination of GG BDNF, AA DAT, and AA COMT with lack of MLIC in PD patients (VIP > 1). Conclusions Our results confirmed the association of rs6265 BDNF (Val66Met) with the risk of PD and suggest a synergic effect of rs6265 BDNF (Val66Met), rs397595 DAT (SLC6A3), and rs4680 COMT (Val158Met) polymorphisms on the occurrence of MLIC.
Liczne badania wskazują, że dopamina (DA) jest ważnym regulatorem funkcji motorycznych, psychologicznych i kognitywnych. Utrzymanie odpowiedniego stężenia DA jest warunkiem prawidłowego działania tych funkcji. W kontroli syntezy DA bierze udział hydroksylaza tyrozynowa (TH). Celem pracy niniejszej pracy jest omówienie regulacji aktywność TH przy współudziale trzech głównych mechanizmów: 1) post-translacyjnego, z chwili na chwilę, poprzez fosforylację różnych miejsc w cząsteczce enzymu oraz 2) post-transkrypcyjnego, przy współudziale czynników transkrypcyjnych i specyficznych miRNAs, oraz 3) mechanizm regulacji zwrotnej z udziałem DA. Istotnymi czynnikami uczestniczącymi pośrednio lub bezpośrednio w tych regulacjach aktywności TH i stężenia DA są BDNF, testosteron, alfa-synukleina oraz kinazy białkowe. Drastyczne obniżenie poziomu DA w układzie pozapiramidowym powoduje upośledzenie czynności motorycznych, psychologicznych i kognitywnych. Zwiększona aktywność fizyczna, w szczególności długotrwałe powtarzany wysiłek fizyczny zwiększając poziom testosteronu i BDNF we krwi, może aktywować zależne od nich szlaki sygnałowe zwiększając aktywność hydroksylazy tyrozynowej, a tym samym podnosić poziom dopaminy w układzie pozapiramidowym.
The aim of this study was to evaluate the effects of sodium phosphate (SP) supplementation on aerobic capacity in hypoxia. Twenty-four trained male cyclists received SP (50 mg·kg−1 of FFM/day) or placebo for six days in a randomized, crossover study, with a three-week washout period between supplementation phases. Before and after each supplementation phase, the subjects performed an incremental exercise test to exhaustion in hypoxia (FiO2 = 16%). Additionally, the levels of 2,3-diphosphoglycerate (2,3-DPG), hypoxia-inducible factor 1 alpha (HIF-1α), inorganic phosphate (Pi), calcium (Ca), parathyroid hormone (PTH) and acid-base balance were determined. The results showed that phosphate loading significantly increased the Pi level by 9.0%, whereas 2,3-DPG levels, hemoglobin oxygen affinity, buffering capacity and myocardial efficiency remained unchanged. The aerobic capacity in hypoxia was not improved following SP. Additionally, our data revealed high inter-individual variability in response to SP. Therefore, the participants were grouped as Responders and Non-Responders. In the Responders, a significant increase in aerobic performance in the range of 3–5% was observed. In conclusion, SP supplementation is not an ergogenic aid for aerobic capacity in hypoxia. However, in certain individuals, some benefits can be expected, but mainly in athletes with less training-induced central and/or peripheral adaptation.
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