ABSTRACT
Genes encoding proteins involved in dopaminergic transmission have been of special interest during the evaluation of candidate genes for Parkinson's disease (PD). The dopamine D2 receptor gene (DRD2) is located on chromosome 11 q22-q23, and several polymorphisms of the gene have been described. The DRD2 gene has a TaqI A restriction fragment length polymorphism that is located in the untranslated region, approximately 10 kilobases from the 3' end of the gene. This polymorphism creates the two alleles A1 (variant) and A2. In this study, we investigated the hypothesis that a TaqI repeat fragment length polymorphism in the dopamine D2 receptor gene may be associated with PD. DNA from 72 patients with PD, classified as definite, probable, or atypical PD, and from 81 controls was genotyped by polymerase chain reaction and gel electrophoresis for the presence of the TaqI A1 polymorphism. The controls were matched for age, race, and geographic origin. There were significant differences in allelic distribution between the overall PD group and control groups (chi2 = 5.009, p = 0.025). When only patients with definite PD were considered an even more significant association was found (chi2 = 8.2121, p = 0.004). Among the overall PD group, the odds ratio for having the variant allele A1 was found to be 2.2 (95% confidence interval, [1.1; 4.4]), whereas it was calculated to be 3.0 (95% confidence interval, [1.4; 6.4]) when only patients with definite PD were considered. The current study showed that there is a statistically significant association between the DRD2 variant allele A1 and PD. This association is most pronounced in patients with definite PD and becomes nonsignificant when the clinical picture is classified as atypical PD.
Subject(s)
Alleles , Chromosomes, Human, Pair 11/genetics , Parkinson Disease/genetics , Polymorphism, Restriction Fragment Length , Receptors, Dopamine D2/genetics , Aged , Aged, 80 and over , Case-Control Studies , Chi-Square Distribution , Female , Humans , Male , Middle Aged , Odds RatioSubject(s)
Cytochrome P-450 CYP2D6/genetics , Risperidone/metabolism , Adolescent , Adult , Cytochrome P-450 CYP2D6/metabolism , Drug Monitoring , Genotype , Humans , Isoxazoles/metabolism , Male , Paliperidone Palmitate , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Pyrimidines/metabolism , Risperidone/therapeutic useABSTRACT
Circadian variations in the interaction between calcium channel blockers and morphine-induced analgesia were determined by the mouse hot-plate test. Calcium channel blockers diltiazem, verapamil, or nicardipine alone did not display any significant analgesic effect, but all of them potentiated morphine-induced analgesia when injected 30 min prior to morphine at most of the injection times. In terms of percent absolute potentiation, they produced more potentiation during the light period than darkness. Their potentiating effects decreased abruptly during darkness, and around the midtime of the dark period no significant potentiation of morphine-induced analgesia was observed. It is concluded that these fluctuations in the magnitude of interaction between calcium channel blockers and morphine must be taken into consideration particularly in studies dealing with the role of calcium in analgesia.
