Development of a Biochip for Analyzing Polymorphism of the Biotransformation Genes

Glotov, Andrey S.; Наседкина, Т. В.; Ivaschenko, T. E.; Urasov, R. A.; Суржиков, С. А.; Pan’kov, S. V.; Чудинов, А. В.; Baranov, V. S.; Zasedatelev, A. S.

doi:10.1007/s11008-005-0050-8

Cited by 28 publications

(5 citation statements)

References 10 publications

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“…On the 3' end, the probes carried a spacer with a free amino group introduced using a 3' Amino Modifier C7 CPG 500 (Glen Research, United States). Oligo nucleotide probe sequences were previously optimized when developing the biochip for the analysis of poly morphisms in biotransformation system genes [15].…”

Section: Methodsmentioning

confidence: 99%

Association of polymorphisms of xenobiotic-metabolizing genes with glucocorticoid-induced osteoporosis in patients with bronchial asthma

et al. 2012

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Investigation of risk factors for glucocorticoid induced (GI) osteoporosis, which is one of the most frequent and serious complications of long term systemic glucocorticoid (SGC) therapy for bronchial asthma, is a topical issue of preventative medicine. In the present work, allele specific hybridization on a bio chip was used to determine the allele and genotype frequencies of eight candidate genes for GI osteoporosis in 137 patients with bronchial asthma receiving long term SGC therapy. The MTHFR polymorphism 677C>T showed a significant association with the proximal femur mineral density (Z score) in patients treated with SGC (nonparametric Kruskal-Wallis ANOVA, p = 0.0013). On the other hand, carriers of the null genotype by the GSTM1 insertion-deletion polymorphism had lower bone mineral density Z scores than carriers of at least one functional GSTM1 allele (Mann-Whitney U test with the Bonferroni correction, p = 0.034). Anal ysis of gene-gene interactions showed that the MTHFR 677C/C/GSTM1 null genotype combination was associated with significantly lower bone mineral density Z scores than other genotype variants (KruskalWallis ANOVA, p = 0.0012). Thus, the MTHFR and GSTM1 alleles can modulate the risk of GI osteoporosis in patients with bronchial asthma, which is very important for the identification of patients at a high risk of osteoporosis among individuals receiving SGC, as well as inhaled glucocorticoids.

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Section: Methodsmentioning

confidence: 99%

Association of polymorphisms of xenobiotic-metabolizing genes with glucocorticoid-induced osteoporosis in patients with bronchial asthma

et al. 2012

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“…Particular attention is focused on the testing of hereditary forms of thrombophilia, for diagnostics of which a special microbiochip called "Fibrochip" was developed [ 27 ]. The clinical trials of the genetic map of reproductive health (GMRH) conducted at the Ott’s Institute of Obstetrics and Gynecology, RAMS, focused primarily on individual disorders, such as endometriosis (prognosis and choice of optimal treatment tactics), inherited thrombophilia factors, miscarriage and placental insufficiency, and gestosis (prediction and prevention).…”

Section: Genetic Passmentioning

confidence: 99%

Genome Paths A Way to Personalized and Predictive Medicine

Baranov

2009

Acta Naturae

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The review is devoted to the impact of human genome research on progress in modern medicine. Basic achievements in genome research have resulted in the deciphering of the human genome and creation of a molecular landmarks map of the human haploid genome (HapMap Project), which has made a tremendous contribution to our understanding of common genetic and multifactorial (complex) disorders. Current genome studies mainly focus on genetic testing and gene association studies of multifactorial (complex) diseases, with the purpose of their efficient diagnostics and prevention . Identification of candidate ("predisposition") genes participating in the functional genetic modules underlying each common disorder and the use of this genetic background to elaborate sophisticated measures to efficiently prevent them constitutes a major goal in personalized molecular medicine. The concept of a genetic pass as an individual DNA databank reflecting inherited human predisposition to different complex and monogenic disorders, with special emphasis on its present state, and the numerous difficulties related to the practical implementation of personalized medicine are outlined. The problems related to the uncertainness of the results of genetic testing could be overcome at least partly by means of new technological achievements in genome research methods, such as genome-wide association studies (GWAS), massive parallel DNA sequencing, and genetic and epigenetic profiling. The basic tasks of genomic today could be determined as the need to properly estimate the clinical value of genetic testing and its applicability in clinical practice. Feasible ways towards the gradual implementation of personal genetic data, in line with routine laboratory tests, for the benefit of clinical practice are discussed.

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“…In the last few years, several biosensors have been developed with the purpose of promoting precision medicine with advantages in terms of efficiency, time and costs of analysis. However, only few studies report the development of miniaturized DNA chip performing allelic variant discrimination to avoid ADRs in oncological patients [ 15 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Development of a Pharmacogenetic Lab-on-Chip Assay Based on the In-Check Technology to Screen for Genetic Variations Associated to Adverse Drug Reactions to Common Chemotherapeutic Agents

et al. 2020

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Background: Antineoplastic agents represent the most common class of drugs causing Adverse Drug Reactions (ADRs). Mutant alleles of genes coding for drug-metabolizing enzymes are the best studied individual risk factors for these ADRs. Although the correlation between genetic polymorphisms and ADRs is well-known, pharmacogenetic tests are limited to centralized laboratories with expensive or dedicated instrumentation used by specialized personnel. Nowadays, DNA chips have overcome the major limitations in terms of sensibility, specificity or small molecular detection, allowing the simultaneous detection of several genetic polymorphisms with time and costs-effective advantages. In this work, we describe the design of a novel silicon-based lab-on-chip assay able to perform low-density and high-resolution multi-assay analysis (amplification and hybridization reactions) on the In-Check platform. Methods: The novel lab-on-chip was used to screen 17 allelic variants of three genes associated with adverse reactions to common chemotherapeutic agents: DPYD (Dihydropyrimidine dehydrogenase), MTHFR (5,10-Methylenetetrahydrofolate reductase) and TPMT (Thiopurine S-methyltransferase). Results: Inter- and intra assay variability were performed to assess the specificity and sensibility of the chip. Linear regression was used to assess the optimal hybridization temperature set at 52 °C (R2 ≈ 0.97). Limit of detection was 50 nM. Conclusions: The high performance in terms of sensibility and specificity of this lab-on-chip supports its further translation to clinical diagnostics, where it may effectively promote precision medicine.

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Development of a Biochip for Analyzing Polymorphism of the Biotransformation Genes

Cited by 28 publications

References 10 publications

Association of polymorphisms of xenobiotic-metabolizing genes with glucocorticoid-induced osteoporosis in patients with bronchial asthma

Association of polymorphisms of xenobiotic-metabolizing genes with glucocorticoid-induced osteoporosis in patients with bronchial asthma

Genome Paths A Way to Personalized and Predictive Medicine

Development of a Pharmacogenetic Lab-on-Chip Assay Based on the In-Check Technology to Screen for Genetic Variations Associated to Adverse Drug Reactions to Common Chemotherapeutic Agents

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