polymorphism-MDR1
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- MeSH
- DNA genetika krev MeSH
- epidemiologické studie MeSH
- finanční podpora výzkumu jako téma MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus genetika účinky léků MeSH
- léková rezistence genetika účinky léků MeSH
- lidé MeSH
- P-glykoprotein genetika účinky léků MeSH
- polymerázová řetězová reakce metody využití MeSH
- polymorfismus genetický fyziologie genetika MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Česká republika MeSH
OBJECTIVES: The aim of prospective study was to evaluate the therapeutic efficacy of piritramide in patients after removal of parathyroid glands in relation to MDR1 genotype. In the treatment of moderate acute postoperative pain, piritramide plays a major role. It is difficult to predict its optimal therapeutic efficacy and tolerability in individual patients. METHODS: We compared the effect of piritramide in 56 patients after surgical removal of parathyroid glands in a prospective study. We evaluated pain intensity, pain difference and sum of pain difference (SPID) using visual analogue scale (VAS in mm) and adverse effects in the relationship with the MDR1 - polymorphism of G2677T/A. RESULTS: In the wild-type group (2677GG), there was maximal pain difference of 30.6 ± 24.9 and SPID of 209.33 ± 95.80 while in genotype 2677TT and 2677GT, the corresponding values were 19.5 ± 25.5 and 147.07 ± 91.38, respectively. In group of patients with wild type of 2677GG genotype, there was 80 % of responders with more than 50 % reduction in VAS as compared to baseline while in group with carriers of 2677T allele, there are only 39 % of responders present (χ² = 5. 83; p = 0.016). Furthermore, the total consumption of piritramide was lower in comparison with the variant-allele carrying group (p = 0.008). The total incidence of adverse drug reactions was observed in 40 % of patients with wild type of 2677GG genotype when compared to 83% in the group carrying the variant allele (χ² = 7.92; p = 0.005). Significantly more patients in the wild-type group were satisfied with postoperative pain treatment in comparison to the variant allele group (χ² = 6. 49; p = 0.0109). CONCLUSION: We observed a better analgesic effect of piritramide and a decreased incidence of side effects in the wild-type genotype (2677GG) group, when compared with variant-allele carrying patients (Tab. 2, Fig. 1, Ref. 7).
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- měření bolesti * MeSH
- opioidní analgetika terapeutické užití MeSH
- P-glykoprotein genetika MeSH
- paratyreoidektomie MeSH
- pirinitramid terapeutické užití MeSH
- polymorfismus genetický * MeSH
- pooperační bolest farmakoterapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: P-glycoprotein (P-gp/MDR1), a member of the ATP-binding cassette (ABC) transporters super family, encoded by the ABCB1/MDR1 gene, is one of suggested respiratory tract protection components, found in various tissues with a barrier function, such as tracheobronchial epithelium and lung parenchyma. As an ATP-dependent pump, P-gp extrudes lipophilic particles out of cells and acts as a gatekeeper against numerous xenobiotics, with a protective role in mediating DNA damage, secretion of toxic compounds, apoptosis and the immune response. Therefore, a presence of MDR1 polymorphisms and altered P-gp expression may be important for pathogenesis of reduced lung inflammatory response on cigarette smoke exposure, as well as for the severity of chronic obstructive pulmonary disease and lung cancer pathogenesis and treatment efficacy. METHODS AND RESULTS: We have analyzed data available from experimental and clinical studies performed to establish the role of MDR1 polymorphisms, especially the 3435C>T variation, and P-gp expression in pathogenesis and clinical outcome of human respiratory diseases. CONCLUSIONS: Although there are indications that altered expression of P-gp and/or polymorphisms of MDR1 gene play an important role in respiratory diseases pathogenesis and treatment, their exact role and relevance are insufficiently investigated, with exception of certain chemotherapeutic agents' efficacy in lung cancer treatment. Further research in this field, including bigger series of patients, is necessary for better understanding of respiratory diseases' pathogenesis and treatment.
- MeSH
- DNA genetika MeSH
- genetická predispozice k nemoci * MeSH
- lidé MeSH
- nemoci dýchací soustavy genetika metabolismus MeSH
- P-glykoprotein biosyntéza genetika MeSH
- P-glykoproteiny genetika metabolismus MeSH
- polymorfismus genetický * MeSH
- regulace genové exprese * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Paroxetine-induced sexual dysfunction represents a frequent treatment complication of otherwise efficient antidepressants. The genetic polymorphism of pharmacokinetic genes may contribute to the occurrence of such dysfunctions. This study presents the effect of MDR1 gene polymorphisms on sexual function in 18 women with bulimia nervosa, 18 women with anxiety disorders, and 19 healthy control subjects. It also deals with the relation between MDR1 gene polymorphisms and paroxetine-induced sexual dysfunction. The results demonstrated that MDR1 G2677T/A gene polymorphism allele carriers treated with paroxetine presented with difficulties with orgasm (p = .008) and lubrication (p < .001).
- MeSH
- antidepresiva druhé generace aplikace a dávkování MeSH
- bulimia nervosa farmakoterapie genetika MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mutace genetika MeSH
- P-glykoprotein genetika MeSH
- polymorfismus genetický * MeSH
- sexuální dysfunkce psychické chemicky indukované genetika MeSH
- studie případů a kontrol MeSH
- úzkostné poruchy farmakoterapie genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: The aim of our study was to evaluate impact of CYP2D6 and MDR1 polymorphisms on the analgesic efficacy of tramadol in patients after a knee arthroscopy. BACKGROUND : Pharmacokinetics of tramadol and its metabolites is stereoselective and displays high interindividual variability correlating with polymorphic CYP2D6 in the population. Available data provide controversial results regarding the analgesic efficacy of tramadol in subjects with different CYP2D6 genotypes. METHODS: Pain intensity was assessed using visual analogue scale at 2 and 24 hours after the knee arthroscopy in 156 patients. Polymorphisms CYP2D6*3,*4,*5,*6, and gene duplication and C3435T in MDR1 gene were analyzed by PCR - RFLP. Results: Mean VAS2h value in the whole study group was 44.0 ± 16.5 mm. Mean pain difference, was lowest in the UM group and highest in the PM group. The pain difference varied significantly among the CYP2D6 subgroups (F = 4.29; p = 0.006) with significant differences between homEM vs hetEM, homEM vs PM, and UM vs PM subgroups. There were no significant differences among MDR1 subgroups with regards of pain difference. Mean tramadol consumption was 2.47 ± 1.17 mg/kg during the 24 h period. There were no significant differences in the drug consumption, reporting of adverse reactions, need for rescue analgesic medication or verbal description of pain among the CYP2D6 or MDR1 genotype subgroups. CONCLUSION: CYP2D6 plays a significant role in tramadol analgesic efficacy. The non-opioid analgesia in PMs was associated with better subjective pain relief in patients after a knee arthroscopy (Tab. 3, Ref. 18).
- MeSH
- artroskopie MeSH
- cytochrom P-450 CYP2D6 genetika MeSH
- dospělí MeSH
- frekvence genu MeSH
- heterozygot MeSH
- kolenní kloub chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- měření bolesti MeSH
- opioidní analgetika terapeutické užití MeSH
- P-glykoprotein genetika MeSH
- polymorfismus genetický MeSH
- pooperační bolest farmakoterapie MeSH
- tramadol terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
ATP Binding Cassette B1 (ABCB1) is a transporter with a broad substrate specificity involved in the elimination of several carcinogens from the gut. Several polymorphic variants within the ABCB1 gene have been reported as modulators of ABCB1-mediated transport. We investigated the impact of ABCB1 genetic variants on colorectal cancer (CRC) risk. A hybrid tagging/functional approach was performed to select 28 single nucleotide polymorphisms (SNPs) that were genotyped in 1,321 Czech subjects, 699 CRC cases and 622 controls. In addition, six potentially functional SNPs were genotyped in 3,662 German subjects, 1,809 cases and 1,853 controls from the DACHS study. We found that three functional SNPs (rs1202168, rs1045642 and rs868755) were associated with CRC risk in the German population. Carriers of the rs1202168_T and rs868755_T alleles had an increased risk for CRC (P(trend) = 0.016 and 0.029, respectively), while individuals bearing the rs1045642_C allele showed a decreased risk of CRC (P(trend) = 0.022). We sought to replicate the most significant results in an independent case-control study of 3,803 subjects, 2,169 cases and 1,634 controls carried out in the North of Germany. None of the SNPs tested were significantly associated with CRC risk in the replication study. In conclusion, in this study of about 8,800 individuals we show that ABCB1 gene polymorphisms play at best a minor role in the susceptibility to CRC.
- MeSH
- alely MeSH
- dospělí MeSH
- genetická predispozice k nemoci * MeSH
- genotyp MeSH
- kolorektální nádory diagnóza genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- modely genetické MeSH
- P-glykoprotein genetika MeSH
- P-glykoproteiny MeSH
- polymorfismus genetický * MeSH
- riziko MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol 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
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- alkylační protinádorové látky škodlivé účinky terapeutické užití toxicita MeSH
- antracykliny škodlivé účinky terapeutické užití toxicita MeSH
- chemické látky - účinky a užití MeSH
- DNA vazebné proteiny genetika účinky léků MeSH
- financování organizované MeSH
- lidé MeSH
- nádory prsu farmakoterapie genetika imunologie MeSH
- P-glykoprotein genetika účinky léků MeSH
- polymerázová řetězová reakce metody využití MeSH
- polymorfismus genetický genetika imunologie účinky léků MeSH
- statistika jako téma metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- abstrakty MeSH