Pharmacogenetics biomarkers of antipsychotics’ safety in adolescents with acute psychotic episode

Currently, there is a lack of pharmacogenetic research of antipsychotics’ safety in children and adolescents with acute psychotic episodes. Genetic polymorphisms of CYP2D6 and ABCB1 are the most likely candidates for such studies. AIM.To establish possible associations of CYP3A, CYP2D6, ABCB1 polymorphisms with safety of antipsychotics of an acute psychotic episode in adolescents during the first 14 days of treatment. MATERIALS AND METHODS. We observed 53 adolescents, hospitalized with acute psychotic episode, during 14 days of treatment. Mean age was 15,08±1,7 years. All patients took antipsychotic as the main drug. The tolerance to antipsychotics was assessed using UKU SERS, SAS, BARS. We collected a buccal epitelium from each patient and genotyped CYP3A4*22 (rs2740574), CYP3A5*3 (6986A>G, rs7767746), CYP2D6*4, *10 (rs3892097, rs1065852), ABCB1 1236C>T (rs1128503), 2677G>T/A (rs2032582), 3435C>T (rs1045642) by real-time PCR. RESULTS. Scores of UKU SERS, SAS, BARS, AIMS scales did not correlated with average doses of antipsychotics. Distribution of genetic polymorphisms were in the Hardy-Weinberg equilibrium. The carriage of CYP2D6*4 was associated with the presence of «Asthenia / Lassitude / lncreased Fatigability» (70% vs. 3.6%, p=0.039), the carriage of CYP2D6*10 was associated with «Increased dream activity» (53.8% vs. 22.5%, p=0.043). The «Increased Duration of Sleep» was more often observed in homozygotes according to the polymorphisms ABCB1 2677G>T/A (50% vs. 15.8%, p=0.006) and 3435C>T (41.7% vs. 8.2%, p=0.007). Carriers of TT polymorphism homozygote ABCB1 2677G>T/A also more frequently noted «Polyuria/polydypsia» (37.5% vs. 5.18%, p=0.045). CONCLUSION.Genetic polymorphisms CYP2D6*4, *10, ABCB1 2677G>T/A and 3435C>T increased a risk of adverse drug effects of antipsychotics in adolescents with acute psychotic episode.

Download Full-text

Analysis of Polymorphisms in Genes Differentially Expressed in the Enamel of Mice with Different Genetic Susceptibilities to Dental Fluorosis

Caries Research ◽

10.1159/000491554 ◽

2018 ◽

Vol 53 (2) ◽

pp. 228-233 ◽

Cited By ~ 4

Author(s):

Senda Charone ◽

Erika Calvano Küchler ◽

Aline de Lima Leite ◽

Mileni Silva Fernandes ◽

Vinicius Taioqui Pelá ◽

...

Keyword(s):

Drinking Water ◽

Real Time ◽

Dna Extraction ◽

Genetic Polymorphisms ◽

Clinical Evaluation ◽

Real Time Pcr ◽

Genomic Dna ◽

Dental Fluorosis ◽

Clinical Aspects ◽

Genomic Dna Extraction

Genes expressed during amelogenesis are candidates to increase the risk of dental fluorosis (DF). Thus, this study aimed to evaluate the association between polymorphisms in enamel development genes and susceptibility to DF in mice. Mice of both sexes, representing strains 129P3/J (n = 20; resistant to DF) and A/J (n = 20; susceptible to DF), were divided into 2 groups. Each strain received a diet with a low concentration of fluoride (F) and drinking water containing 0 or 50 mg/L of F for 6 weeks. Clinical evaluation and analysis of Vickers enamel microhardness of the incisors were performed. Livers were collected for genomic DNA extraction. Seventeen genetic polymorphisms in Amelx, Ambn, Ambn, Col14a1, Col1a1, Col5a2, Enam, Fam20a, Fam83h, Foxo1, Klk4, Mmp20, Serpinf1, Serpinh1, Smad3, Tuft1, and Wdr72 were genotyped by real-time PCR using Taqman chemistry. Overrepresentation of alleles and genotypes in DF was evaluated using the χ2 test with an alpha of 5%. The clinical aspects of the enamel and the surface enamel microhardness confirmed the DF condition. In the polymorphisms rs29569969, rs13482592, and rs13480057 in Ambn, Col14a1, and Mmp20, respectively, genotype and allele distributions were statistically significantly different between A/J and 129P3/J strains (p < 0.05). In conclusion, polymorphisms in Ambn, Col14a1, and Mmp20 are associated with the susceptibility to DF.

Download Full-text

Reliability of non-invasively acquired human genomic DNA as a substrate for real-time PCR-assisted analysis of genetic polymorphisms

Archives of Toxicology ◽

10.1007/s00204-004-0554-3 ◽

2004 ◽

Vol 78 (7) ◽

Cited By ~ 7

Author(s):

T. Neuhaus ◽

G. Geisen ◽

H.M. Bolt ◽

V. Janzen ◽

A. Kraemer ◽

...

Keyword(s):

Real Time ◽

Genetic Polymorphisms ◽

Real Time Pcr ◽

Genomic Dna ◽

Human Genomic ◽

Assisted Analysis ◽

Human Genomic Dna

Download Full-text

Polymorphisms in Nonamelogenin Enamel Matrix Genes Are Associated with Dental Fluorosis

Caries Research ◽

10.1159/000479826 ◽

2017 ◽

Vol 52 (1-2) ◽

pp. 1-6 ◽

Cited By ~ 14

Author(s):

Erika Calvano Küchler ◽

Carolina Dea Bruzamolin ◽

Marjorie Ayumi Omori ◽

Marcelo C. Costa ◽

Leonardo Santos Antunes ◽

...

Keyword(s):

Real Time ◽

Genetic Polymorphisms ◽

Real Time Pcr ◽

Genomic Dna ◽

Dental Fluorosis ◽

Permanent Teeth ◽

Enamel Matrix ◽

Water Supplies ◽

Allele Distribution

The aim of this study was to evaluate whether genetic polymorphisms in AMELX, AMBN, ENAM, TFIP11, and TUFT1 genes are associated with dental fluorosis (DF). A total of 1,017 children from 2 Brazilian cohorts were evaluated. These populations lived in cities with fluoridation of public water supplies. DF was assessed in erupted permanent teeth using the modified Dean index. The polymorphisms rs946252, rs12640848, rs4694075, rs5997096, and rs4970957 were analyzed by real-time PCR from genomic DNA. Associations between DF, genotype, and allele distribution were evaluated using the χ2 test, with an alpha of 5%. The polymorphisms rs4694075, rs5997096, and rs4970957 in AMBN, TFIP11, and TUFT1 were associated with DF (p < 0.05). In conclusion, enamel matrix genes are associated with DF.

Download Full-text

Pharmacogenetic research in Kazakhstan

Central Asian Journal of Global Health ◽

10.5195/cajgh.2013.87 ◽

2014 ◽

Vol 2 ◽

Author(s):

Elena Zholdybayeva ◽

Aisha Iskakova ◽

Aliya Romanova ◽

Erlan Ramanculov ◽

Kuvat Momynaliev

Keyword(s):

Real Time ◽

Real Time Pcr ◽

Venous Blood ◽

Drug Dosage ◽

Direct Dna Sequencing ◽

Allelic Frequencies ◽

Pharmacogenetic Research ◽

Kazakh Population ◽

Pharmacogenomic Studies ◽

Selection Of

Introduction: Pharmacogenomics is an emerging field of medicine that combines genetics and pharmacology. Pharmacogenomic research is relatively new in Kazahkstan, but, in recent years, significant progress has been made in this field. The National Scientific Laboratory for Biotechnology has launched several government-funded research projects focused on finding genetic markers that determine susceptibility to various drugs. Another goal of pharmacogenetic research in the laboratory is to find the pharmacogenomic markers that target cardiovascular diseases, accounting for allelic frequencies in selected genes in the Kazakh population. In addition, pharmacogenomic testing kits allow patients to choose the drug dosage. For example, the drug Warfarin has been developed within the framework of the "Technology Commercialization Project,” funded jointly by the Ministry of Education and Science of the Republic of Kazakhstan and the World Bank.Material and methods: The pharmacogenomic studies were conducted using the real-time PCR and direct DNA sequencing. DNA was isolated from venous blood or buccal cells, collected from patients.Results: To date, we have identified the most promising areas of research in the field of pharmacogenomics in Kazakhstan. The allelic frequencies of a number of polymorphisms in the Kazakh population have been calculated (CYP2C9, CYP2C19, CYP3A4, VKORC1, CYP4F2, GGCX, CYP2D6, CYP1A2, NAT2, GSTP1, SLC47A1). A unique repository of DNA samples was established and is being replenished during the implementation of aforementioned projects. Development of the testing kit for individual selection of Warfarin dosage is nearing completion. A patent, named "Method of Selection Based Dose Warfarin Genotyping for the Kazakh Population" has been recently obtained. An application for another patent, titled "Express Method of Correction of Warfarin Dosing, Based on Real-time PCR" has received positive evaluation. The results of domestic pharmacogenomic studies will allow a more rational selection of drugs and their dosage regimens specific to the Kazakh population.

Download Full-text

Evaluation of drug effects on Toxoplasma gondii nuclear and plastid DNA replication using real-time PCR

Parasitology Research ◽

10.1007/s00436-010-1792-3 ◽

2010 ◽

Vol 106 (5) ◽

pp. 1257-1262 ◽

Cited By ~ 4

Author(s):

Qing Zhao ◽

Ming Zhang ◽

Lingxian Hong ◽

Kefu Zhou ◽

Yuguang Lin

Keyword(s):

Dna Replication ◽

Toxoplasma Gondii ◽

Real Time ◽

Real Time Pcr ◽

Drug Effects ◽

Plastid Dna

Download Full-text

Geographic distribution of the 3435C>T polymorphism of the MDR1 gene in Peruvian populations

Drug Metabolism and Personalized Therapy ◽

10.1515/dmpt-2018-0041 ◽

2019 ◽

Vol 34 (3) ◽

Author(s):

Edward Valencia Ayala ◽

Pool Marcos Carbajal ◽

Eduardo Barbosa Coelho ◽

Jose Sandoval Sandoval ◽

Alberto Salazar Granara

Keyword(s):

Genetic Polymorphisms ◽

Geographic Distribution ◽

Allele Frequencies ◽

Genotype Frequency ◽

Mdr1 Gene ◽

Frequency Distributions ◽

Weinberg Equilibrium ◽

Pearson Test ◽

Hardy Weinberg Equilibrium ◽

Genotype And Allele Frequencies

Abstract Background The MDR1 gene presents several genetic polymorphisms with pharmacological implications. Therefore, the aim of the present study is to establish the genotype and allele frequencies of 3435C>T polymorphism of MDR1 gene into Peruvian populations (Coastal, Andean and Amazonian ecoregions), even considering the altitude (lowland <2500 m and highland >2500 m). Methods The polymorphism was analyzed by TaqMan genotyping assays in a group of 181 healthy unrelated Peruvian individuals. The comparison of genotype and allele frequencies of 3435C>T polymorphism was made with the Pearson test (X2), and, to calculate the genotype distributions, the Hardy-Weinberg equilibrium (HWE) was used. Results In all populations evaluated in this study, the genotype frequency distributions met HWE assumptions. The comparison between genotype and allele frequencies showed significant differences (p < 0.05), when the Andean, Coastal and Amazonian populations were compared. Also, significant differences (p < 0.05) were obtained when these populations were compared considering their altitudes. Likewise, in comparison with countries like USA, Finland, Nigeria and Kenya, the results showed significant differences (p < 0.05). Conclusions This investigation allowed us to establish the genotype and allele frequencies of 3435C>T polymorphism in different Peruvian populations, considering the geographic localization and even the altitude.

Download Full-text