OPRM1 Dotaz Zobrazit nápovědu
Příčiny schizofrenie jsou dnes všeobecně spojovány s poruchami ve vývoji mozku. To mimo jiné podporují i práce poukazující na genetický základ abnormálního neurovývoje u schizofrenie. V naší asociační studii jsme se zabývali vztahem polymorfizmu A118G genu pro OPRMl ke schizofrenii. Z výsledků je patrný statisticky významný rozdíl alelických i genotypových frekvencí mezi kontrolní skupinou a schizofreniky. Dle současných poznatků se nabízí příčinná souvislost mezi polymorfizmem genu pro OPRMl a myelinizací neuronů CNS, a to prostřednictvím regulace exprese OPRMl receptoru na povrchu oligodendrocytů. Proces myelinizace se zdá být významným faktorem patogeneze schizofrenie.
Etiology of schizophrenia is associated with disruptions in neural development. Neurodevelopment theory is supported by quite strong genetic evidence. In our study, we studied the relationship between functional A118G polymorphism of OPRM1 gene and schizophrenia. The results showed statistically significant difference of allelic and genotypic frequencies between control and schizophrenic males. According recent knowledge, we suppose that OPRM1 gene polymorphism can influence myelinization of CNS neurons through regulation of expression of OPRM1 receptors on oligodendrocytes. Process of myelinization of CNS neurons seems to be an important factor of pathogenesis of schizophrenia.
- Klíčová slova
- asociační studie, polymorfizmus, OPRM1, gen,
- MeSH
- DNA MeSH
- schizofrenie MeSH
- Publikační typ
- abstrakty MeSH
Abnormality v neurovývoji patří mezi nejvíce přijímané hypotézy etiologie schizofrenie. Existují důkazy, že genetické faktory mohou ovlivňovat abnormální neu-rovývoj u této choroby. Naše studie byla zaměřena na vztah mezi funkčním po-lymorfismem A118G genu pro OPRM1 a schizofrenií na skupině 227 mužů. V naší asociační studii jsme objevili statisticky signifikantní rozdíl alelických a genotypových frekvencí mezi skupinami mužů z kontrolní skupiny a mužů schizofreniků. S přihlédnutím k současným poznatkům se domníváme, že polymorfismus genu pro OPRM1 může ovlivňovat myelinizaci neuronů v CNS prostřednictvím regulace exprese OPRM1 receptoru na povrchu oligodendrocytů. Myelinizace neuronů centrální nervové soustavy se jeví jako důležitý faktor patogeneze schizofrenie.
An abnormality in neurodevelopment is one of the most accepted etiologic hypotheses in schizophrenia. There is strong evidence that genetic factors may influence abnormal neurodevelopment in this disease. Our study was focused on the relationship between functional AI 18G polymorphism of OPRM1 gene and schizophrenia on the group of 227 males. In our association study we found statistically significant difference of allelic and genotypic frequencies between control and schizophrenic males. According recent knowledge, we hypothesize that OPRM1 gene polymorphism can influence myelinization of CNS neurons through of regulation of expression of OPRM1 receptors on oligodendrocytes. The myelinization of CNS neurons seems to be one of important factor of pathogenesis of schizophrenia.
- MeSH
- celogenomová asociační studie metody využití MeSH
- centrální nervový systém abnormality patologie růst a vývoj MeSH
- DNA genetika krev MeSH
- dospělí MeSH
- financování organizované MeSH
- lidé MeSH
- polymerázová řetězová reakce metody využití MeSH
- polymorfismus genetický genetika MeSH
- receptory opiátové mu genetika MeSH
- schizofrenie diagnóza etiologie genetika MeSH
- statistika jako téma MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
Schizophrenia is ranked among multifactor diseases in whose pathogenesis, besides environmental factors, an interplay of functional polymorphisms of a larger number of candidate genes is involved. Neurodevelopmental abnormities are among the most accepted hypotheses in the etiology of schizophrenia. Recently, the role of oligodendrocytes in the development of the cortex has been cited repeatedly. During their various phases of differentiation oligodendrocytes present on their surfaces diverse receptors, among others the mu-opioid receptor (OPRM1). The study was focused on the relationship between the functional A118G polymorphism of the OPRM1 gene (rs1799971) and schizophrenia in groups of 130 male patients and 452 male controls. An association study revealed yet unpublished statistically significant difference of allelic and genotypic frequencies between the control and patient groups. According to our present knowledge, we assume that the OPRM1 gene polymorphism can influence the myelination of CNS neurons through regulations of expression of OPRM1 receptors on surfaces of oligodendrocytes. The neuronal myelination seems to be one of the important factors in the pathogenesis of schizophrenia.
The aim of this study was to evaluate the association between OPRM1 and ABCB1 polymorphisms on pain relief with epidural sufentanil in 69 patients after rectosigma resection for cancer. The median number of injections (SD) 2.31 (1.36), IQR=1, required by 118AA subjects was significantly lower in comparison with 118AG group 5.25 (3.13), IQR=6.5, (chi(2)=9.75, p=0.001); correspondingly median drug consumption of 1.16 (0.79), IQR=1.083, defined daily doses (DDD) was significantly less in the 118AA group in comparison with 2.14 (1.17), IQR=2.23, DDD in 118AG subjects, (chi(2)=7.00, p=0.008). Opioid-induced adverse effects were observed in 15 % and 33 % of patients in 118AA and 118AG groups, respectively (chi(2)=8.16, p=0.004). The median number of injections (SD) required by women and men was 3.30 (2.16), IQR=2, and 2.80 (1.59), IQR=1, respectively (chi(2)=6.25, p=0.012). Opioid-induced adverse effects were observed in 26 % and 12 % of women and men, respectively (chi(2)=5.49, p=0.011). Heterozygotes of OPRM1 polymorphism and women were more difficult to treat subpopulations that required higher doses of rescue analgesic medication and suffered more adverse effects.
- MeSH
- epidurální analgezie metody MeSH
- kolorektální nádory chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- management bolesti metody MeSH
- opioidní analgetika aplikace a dávkování MeSH
- P-glykoproteiny genetika MeSH
- polymorfismus genetický fyziologie MeSH
- pooperační bolest farmakoterapie MeSH
- prospektivní studie MeSH
- receptory opiátové mu genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sufentanil aplikace a dávkování MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Genetic factors may contribute to the differential response to opioids. The aim of this study was to evaluate the association between polymorphisms of µ1-opioid receptor gene OPRM1 (rs1799971), and P-glycoprotein transporter gene ABCB1 (rs1045642, rs2032582), and piritramide efficacy under postoperative patient-controlled analgesia (PCA). In 51 patients, OPRM1 variant was associated with decreased efficacy in early postoperative period evidenced by sum of pain intensity difference in the 0-6 h postoperative period (SPID(0-6)), (F=3.27, p=0.029). Mean (SD) SPID(0-6) was observed in the 118AA genotype 22.9 (6.1) mm, which was significantly higher from the 118GG genotype 10.0 (4.4) mm, p=0.006. The lowest cumulative dose was recorded in 118AA genotype 19.1 (9.8) mg, which was significantly less than in the 118GG genotype group 36.6 (6.1) mg, p=0.017. Opioid-induced adverse effects were observed in 11, 30, and 100 % of patients in 118AA, 118AG, and 118GG genotype groups, respectively (p<0.05). Piritramide efficacy and safety was not significantly affected by ABCB1 (rs1045642, rs2032582) polymorphisms. Variant OPRM1 118G allele is associated with decreased acute postoperative pain relief after piritramide. Decreased efficacy leads to higher drug consumption under PCA settings, which however, does not fully compensate insufficient pain relief, but increases incidence of adverse effects.
- MeSH
- dospělí MeSH
- jednoduchá slepá metoda MeSH
- lidé středního věku MeSH
- lidé MeSH
- měření bolesti účinky léků metody MeSH
- opioidní analgetika farmakologie terapeutické užití MeSH
- P-glykoproteiny genetika MeSH
- pirinitramid farmakologie terapeutické užití MeSH
- polymorfismus genetický genetika MeSH
- pooperační bolest diagnóza farmakoterapie genetika MeSH
- prospektivní studie MeSH
- receptory opiátové mu genetika MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
The aim of our study was to evaluate possible effect of ABCB1, and OPRM1 polymorphisms on the efficacy and safety of remifentanil in women undergoing elective cesarean section under general anesthesia. Women received remifentanil (1 microg/kg i.v.) 30 s prior to the induction to standardized general anesthesia. The ABCB1 (rs2032582, rs1045642) and OPRM1 (rs1799971) polymorphisms were analyzed from maternal peripheral blood. The basal hemodynamic and demographic parameters in the study population (n=54) were similar in all the subgroups. The median +/- SD increase of systolic blood pressure at 5 min from the baseline was practically completely abolished in homozygous carriers of ABCB1 variants in comparison with wild-type subjects -2.67+/-25.0 vs. 16.57+/-15.7 mm Hg, p<0.05 for rs2032582, and 2.00+/-23.9 vs. 22.13+/-16.8 mm Hg, p<0.05, for rs1045642, respectively. While no neonate belonging to ABCB1 wild-type homozygous or OPRM1 variant carrying mothers needed any resuscitative measure, 10.5 % of the neonates belonging to OPRM1 wild-type homozygous mothers received resuscitative support similarly as 11.1 %, and 12.5 % of neonates of mothers carrying variants of rs2032582, and rs1045642, respectively. Decreased stabilizing effects of remifentanil on maternal hemodynamics has been observed in ABCB1 wild type mothers, while the adaptation of the neonates was clinically worse in OPRM1 wild type, and ABCB1 variant allele carriers.
- MeSH
- anestetika intravenózní škodlivé účinky terapeutické užití MeSH
- císařský řez * škodlivé účinky MeSH
- dospělí MeSH
- jednonukleotidový polymorfismus genetika MeSH
- krevní tlak účinky léků fyziologie MeSH
- lidé MeSH
- novorozenec MeSH
- P-glykoproteiny genetika MeSH
- piperidiny škodlivé účinky terapeutické užití MeSH
- receptory opiátové mu genetika MeSH
- srdeční frekvence účinky léků fyziologie MeSH
- těhotenství MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The single nucleotide polymorphism (SNP) A118G (rs1799971) in the Mu Opioid Receptor 1 (OPRM1) gene is associated with significant variations in analgesic doses and adverse effects of opioids. The A118G OPRM1 allele distributions vary significantly between different populations worldwide. The study aimed to assess the allele frequency and genotype distribution of OPRM1 A118G SNP in Saudis. This cross-sectional study included 124 healthy Saudis (62 males and 62 females) visiting the King Abdulaziz University Hospital in Jeddah, Saudi Arabia. The Oragene®-DISCOVER (OGR-600) kits were used to collect saliva samples from the participants. Polymerase chain reaction-restriction fragment length polymorphism was utilized to assess the SNP. Among the tested population, 79.03% (95% C.I. 70.81-85.82) were homozygous wild-type A118A, 16.13% (95% C.I. 10.14-23.80) were heterozygous A118G, and 4.84% (95% C.I. 1.80-10.23) were homozygous mutant G118G. OPRM1 A118G polymorphism allele frequencies were 87% (95% C.I. 79.89-92.44) and 13% (95% C.I. 7.56-20.11) for the 118A and 118G alleles, respectively. A higher frequency of the OPRM1 118G allele was present in females, 21% (95% C.I. 11.66-33.17) compared to males, 5% (95% C.I. 1.01-13.50). Relative to other Asian countries, the Saudi population showed a low prevalence of the OPRM1 A118G polymorphism, with a higher frequency of the 118G allele in females. Our research will contribute to the existing knowledge on the prevalence of OPRM1 A118G polymorphism, which could be considered for the personalized prescribing of opioid analgesics.
- MeSH
- frekvence genu MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus * genetika MeSH
- lidé MeSH
- opioidní analgetika * MeSH
- průřezové studie MeSH
- receptory opiátové mu genetika MeSH
- receptory opiátové MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Saudská Arábie MeSH
AIMS: The aim of this study was to compare the efficacy, consumption and safety after piritramide administered either intramuscularly (IM) on demand or via patient-controlled intravenous analgesia (PCA) and to examine the impact of OPRM1 and ABCB1 gene polymorphisms on the drug efficacy/safety in both regimens. METHODS: One hundred and four patients scheduled for elective inguinal hernioplasty received piritramide with PCA or IM for postoperative pain management. We evaluated piritramide consumption, pain intensity using visual analogue scale (VAS) and adverse effects. RESULTS: Median (IQR) piritramide consumption was 18.5 (13.5-31.2) and 15.0 (15.0-15.0) mg in the PCA and IM groups, respectively (P=0.0092). The respective values of area under the VAS2-16-time curve were 40 and 280 mm.h (P=0.0027). Opioid-induced adverse effects were more frequent in the PCA than in the IM group. Variant OPRM1 allele was associated with decreased pain relief, increased opioid consumption and increased incidence of adverse effects, while ABCB1 polymorphisms showed no impact on the observed parameters. CONCLUSIONS: We observed higher piritramide consumption, better pain relief and slightly worse safety profile in the PCA group compared with IM administration. Variant OPRM1 118G allele carriers required higher opioid dosing and suffered from more adverse effects, however, the differences between genotypes have been less pronounced in the PCA patients likely due to improved pain management via PCA.
- MeSH
- lidé MeSH
- opioidní analgetika MeSH
- P-glykoproteiny genetika MeSH
- pacientem kontrolovaná analgezie * MeSH
- pirinitramid * terapeutické užití MeSH
- polymorfismus genetický MeSH
- pooperační bolest farmakoterapie MeSH
- receptory opiátové mu terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Our aim was to describe the effect of dosing and genetic factors on sufentanil- and midazolam-induced analgosedation and withdrawal syndrome (WS) in pediatric population. Analgosedation and withdrawal syndrome development were monitored using COMFORT-neo/-B scores and SOS score. Length of therapy, dosing of sufentanil and midazolam were recorded. Genotypes of selected candidate polymorphisms in CYP3A5, COMT, ABCB1, OPRM1 and PXR were analysed. In the group of 30 neonates and 18 children, longer treatment duration with midazolam of 141 h (2 - 625) vs. 88 h (7 - 232) and sufentanil of 326.5 h (136 - 885) vs. 92 h (22 - 211) (median; range) was found in the patients suffering from WS vs. non-WS group, respectively. Median midazolam cumulative doses were in the respective values of 18.22 mg/kg (6.93 - 51.25) vs. 9.94 mg/kg (2.12 - 49.83); P=0.03, and the respective values for sufentanil were 88.60 microg/kg (20.21 - 918.52) vs. 21.71 microg/kg (4.5 - 162.29); P<0.01. Cut off value of 177 hours for sufentanil treatment duration represented predictive factor for WS development with 81 % sensitivity and 94 % specificity. SNPs in the candidate genes COMT, PXR and ABCB1 affected the dosing of analgosedative drugs, but were not associated with depth of analgosedation or WS. Cumulative dose and length of analgosedative therapy with sufentanil significantly increases the risk of WS in critically ill neonates and children.
- MeSH
- abstinenční syndrom diagnóza genetika MeSH
- adjuvancia anestetická aplikace a dávkování škodlivé účinky MeSH
- dítě MeSH
- farmakogenetika metody MeSH
- genetická variace genetika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- kojenec MeSH
- lidé MeSH
- midazolam aplikace a dávkování škodlivé účinky MeSH
- novorozenec MeSH
- pediatrie metody MeSH
- sufentanil aplikace a dávkování škodlivé účinky MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
