BACKGROUND: Several studies indicated that antipsychotic treatment response and side effect manifestation can be different due to inter-individual variability in genetic variations. AIM OF THE STUDY: Here we perform a case-control study to explore a potential association between schizophrenia and variants within the antipsychotic drug molecular targets (DRD1, DRD2, DRD3, HTR2A, HTR6) and metabolizing enzymes (CYP2D6, COMT) genes in Armenian population including also analysis of their possible relationship with disease clinical symptoms. METHODS: A total of 18 SNPs was studied in patients with schizophrenia (n = 78) and healthy control subjects (n = 77) using MassARRAY genotyping. RESULTS: We found that two studied genetic variants, namely DRD2 rs4436578*C and HTR2A rs6314*A are underrepresented in the group of patients compared to healthy subjects. After the correction for multiple testing, the rs4436578*C variant remained significant while the rs6314*A reported borderline significance. No significant differences in minor allele frequencies for other studied variants were identified. Also, a relationship between the genotypes and age of onset as well as disease duration has been detected. CONCLUSIONS: The DRD2 rs4436578*C genetic variant might have protective role against schizophrenia, at least in Armenians.
- MeSH
- antipsychotika terapeutické užití MeSH
- cytochrom P-450 CYP2D6 genetika MeSH
- dopamin genetika metabolismus MeSH
- dospělí MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- genetické asociační studie MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus * MeSH
- katechol-O-methyltransferasa genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolické sítě a dráhy genetika MeSH
- mladý dospělý MeSH
- receptory dopaminové genetika MeSH
- receptory serotoninové genetika MeSH
- schizofrenie farmakoterapie genetika MeSH
- senioři MeSH
- serotonin genetika metabolismus MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND AND AIMS: Dysregulation of cell-mediated immune response likely plays a role in the pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), but it has not yet been fully established. The aim of this study was to assess the intracellular cytokine production in patients with AAV at different stages of the disease, in particular, in relation to the long-term prognosis. METHODS: We included 69 patients with AAV and 24 healthy controls. Using flow cytometry, the following intracellular cytokines (IC) were measured in all patients: interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin-2 and interleukin-4 in CD3+T cells and interleukin-10 (IL-10) and interleukin 12 (IL-12) in monocytes. Patients were then prospectively followed for a median of 43 months and cytokine production was related to the long-term prognosis. RESULTS: When compared to healthy controls, increased IL-12 production was observed in AAV patients, both active (p<0.01) and in remission (p<0.05). In remission, increased IFN-gamma production was also found (p<0.01). IL-10 production was higher in active patients than in patients in remission (p<0.05) but did not differ from controls. Patients in remission who developed a relapse during follow-up had significantly lower IL-10 production than those without relapse (p<0.01). Results of this prospective study of IC production in AAV confirm findings of previous studies measuring circulating cytokine levels. CONCLUSIONS: Activation of the immune system in AAV patients is noticeable even in remission. Patients with AAV display increased IL-12 production, which seems to be counterbalanced by IL-10. Low IL-10 levels in remission are associated with a higher relapse rate in the long-term follow-up.
- MeSH
- cytokiny imunologie MeSH
- dospělí MeSH
- interleukin-10 imunologie MeSH
- interleukin-12 imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- prospektivní studie MeSH
- protilátky proti cytoplazmě neutrofilů imunologie krev MeSH
- recidiva MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vaskulitida imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
BACKGROUND: Clinical experience with mycophenolate mofetil (MMF) in glomerulonephritis still remains limited. METHODS: In order to assess the experience of one center with the efficacy and tolerability of MMF in patients with glomerulonephritis, we performed a retrospective 6-year analysis of 68 patients treated by MMF for glomerular disease, mainly anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV: n=34) and systemic lupus erythematosus and lupus nephritis (SLE: n=24). Indications were maintenance treatment in 40% of patients, induction treatment in patients not tolerating cyclophosphamide in 27%, and disease relapse in 33%. Mean treatment duration was 11.5 months. RESULTS: Efficacy endpoints were serum creatinine, urinary protein excretion, and steroid dose. In AAV patients, MMF was associated with significant improvement in 18%, partial improvement in 26%, stabilization in 29%, and disease progression in 12%; adverse event dropouts totalled 15%. In SLE, the respective figures were 30, 22, 9, and 22%, with 17% adverse event dropouts. The most frequent side effects were gastrointestinal events (n=7) and infections (n=3). None was life-threatening and there were no deaths. CONCLUSIONS: MMF, in the relatively low doses used, was safe and effective, stabilizing or improving AAV in 73% of patients and SLE in 61%. Further prospective randomized controlled trials with MMF in renal vasculitis and lupus nephritis are clearly warranted.
- MeSH
- autoprotilátky imunologie MeSH
- imunosupresiva škodlivé účinky terapeutické užití MeSH
- kyselina mykofenolová analogy a deriváty škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- nefritida při lupus erythematodes farmakoterapie komplikace MeSH
- neutrofily imunologie MeSH
- retrospektivní studie MeSH
- systémový lupus erythematodes farmakoterapie imunologie MeSH
- vaskulitida farmakoterapie imunologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
