CYP2D6 Genotype in Relation to Liver Toxicity Due to Tetrabenazine in Iraqi Patients with Hyperkinetic Movement Disorders

The common types of movement disorders are ; dystonia which is a syndrome of repetitive muscle contractions. While , Huntington disease is autosomal dominant progressive neurodegenerative disorder, which is characterized by involuntary movements (“chorea”). Tetrabenazine therapy has been shown to effectively control this movements compared with placebo. Design the proper dosing approach for patients treated with tetrabenazine with genotype polymorphisms and their hepatic effect on patients. A prospective case controlled study was carried on 50 patients whom divided into 2 groups :first group involved 25 patients who had chorea, and group 2 included patients with dystonia, whom treated with (tetrabenazine) for three months. In addition to control group involved 25 healthy subjects . Blood samples were collected at the beginning and after three months to assess liver function in relation to genetic polymorphism of CYP 450 2D6 enzyme for both groups and measuring the plasma concentration of tetrabenazine , alpha and beta dyhdrotetrabenazine. The results show a significant CYP 450 2D6 enzyme polymorphism. And elevations of liver enzymes in the patient indicate hepatotoxicity of tetrabenazine and its metabolites, Determination a genotype of the CYP 450 2D6 genes in Iraqi patients, in relation to the safety and efficacy of tetrabenazine .

Growth hormone locus polymorphism in Ongole Grade and Fries Holland Grade bulls and its implications in the digestibility of feed

This research aimed to analyze polymorphism of the growth hormone (GH) gene and its implication on digestibility of low and high quality feed. Forty bulls Ongole Grade (OG) and 30 bulls Fries Holland Grade (FHG) had been selected and subjected for an experiment to measure body weight gain, dry matter intake, feed efficiency and feed digestibility. The treatment was crude fibrous feed from various plants with a fibre weight of 15% (P1: low quality) and 22.5% (P2: high quality). The 389 bp of GH gene was amplified (F = 5'-CCCACGGGAGAGAATGAGGC–3'; dan R = 5'-TGAGGAACTGCAGGGGGPA-3') and digested using Msp1 restriction enzyme. Polymorphism between OC and HFC bulls was 45%. The FHG bulls' weight gain were significantly higher than of OC (P<0.05) at first to third week, but become similar (P>0.05) at fourth week. It was concluded that the polymorphism between FHG and OC was high and HFC have a growth response and feed efficiency higher than those of OC.

The protected phosphoglucomutase polymorphism of the Pompeii worm Alvinella pompejana and its variant adaptability is only governed by two QE mutations at linked sites

The polychaete Alvinella pompejana lives exclusively on the walls of deep-sea hydrothermal vents along the East Pacific Rise. This environment is considered as extreme and highly variable and the worm displays specific adaptations to withstand high temperature and hypoxia. Previous studies revealed the existence of a balanced polymorphism on the enzyme phosphoglucomutase associated with differences in the thermal habitat of the worm. Allozymes 90 and 100 exhibited different optimal enzyme activities and thermostabilities. The exploration of the mutational landscape for allozyme variation of the phosphoglucomutase1 revealed the maintenance of four highly divergent allelic lineages that encode the three most frequent electromorphs, these alleles occurring at different frequencies in populations over the worm’s geographic range. Enzyme polymorphism is only governed by two linked amino-acid replacements located in exon 3 (E155Q and E190Q). Unlike other studies dealing with the non-synonymous variations of the Pgm genes, these substitutions are not linked to other cryptic amino-acid polymorphisms. Overdominance under specific environmental ‘hot’ conditions should represent the most likely way for the long-term persistence of these isoforms. Using directed mutagenesis, overexpression of the three recombinant variants allowed us to test the additive effect of these two mutations on the biochemical properties of this enzyme. Results are coherent with those previously obtained from native proteins and reveal a thermodynamic trade-off between the protein thermostability and catalysis, which is likely to explain the long-term selection of these functional phenotypes before their geographic separation across the Equator with the emergence of a barrier to dispersal, about 1.2 Mya.

Studies on polymorphism of enzyme systems in populations of Apis florea F. (Hymenoptera: Apidae) from Chandigarh and foothills of Himachal Pradesh, North West India

Biochemical characterization and enzyme polymorphism are useful tools in establishing intraspecific diversity in insect populations. The populations of Apis florea F. adult workers were selected from six varied topographic and climatic places of north western India including Chandigarh plain and foothills of Himachal Pradesh. These honey bees were analysed for proteome profile by SDS-Polyacrylamide gel electrophoresis (PAGE). Further four enzyme systems namely malate dehydrogenase (MDH), alcohol dehydrogenase (ADH), esterase (EST) and hexokinase (HK) were analysed for enzyme polymorphism and isozymic variability in all the populations by running native PAGE and staining with specific substrate stains on the gels. Sixteen protein bands were reported in each population of A. florea using SDS PAGE and no difference was found in banding pattern of proteins of the populations studied. Enzymes stained on native PAGE from whole body homogenates revealed single isozymic form of ADH, two isozymic forms each of EST and MDH and three isozymic forms of HK in all the populations of A. florea collected from different study regions. There was significant difference in specific activity of enzymes from different regions but no polymorphism was found for the enzymes studied. Small changes in Rf values were found in the isozymes of the enzymes. The results suggest that none of these enzyme systems could be used as marker to differentiate the species at intraspecific level as the enzyme MDH, ADH, EST and HK did not exhibit polymorphism in A. florea from studied regions. In conclusion a single species of A. florea persisted throughout the area studied. However the slight changes in mobilities of individual bands and also changes in specific activity of enzymes reflect the adaptation ability of the bee according to climate variations.