Open Access
Pharmacogenetics of vascular risk factors in Alzheimer's disease
(MDPI, 2018-01-03) Cacabelos, Ramón; Meyyazhagan, Arun; Carril, Juan Carlos; Cacabelos, Pablo; Teijido Hermida, Óscar; Ciencias de la Salud; Osasun Zientziak
Alzheimer's disease (AD) is a polygenic/complex disorder in which genomic, epigenomic, cerebrovascular, metabolic, and environmental factors converge to define a progressive neurodegenerative phenotype. Pharmacogenetics is a major determinant of therapeutic outcome in AD. Different categories of genes are potentially involved in the pharmacogenetic network responsible for drug efficacy and safety, including pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes. However, most drugs exert pleiotropic effects that are promiscuously regulated for different gene products. Only 20% of the Caucasian population are extensive metabolizers for tetragenic haplotypes integrating CYP2D6-CYP2C19-CYP2C9-CYP3A4/5 variants. Patients harboring CYP-related poor (PM) and/or ultra-rapid (UM) geno-phenotypes display more irregular profiles in drug metabolism than extensive (EM) or intermediate (IM) metabolizers. Among 111 pentagenic (APOE-APOB-APOC3-CETP-LPL) haplotypes associated with lipid metabolism, carriers of the H26 haplotype (23-TT-CG-AG-CC) exhibit the lowest cholesterol levels, and patients with the H104 haplotype (44-CC-CC-AA-CC) are severely hypercholesterolemic. Furthermore, APOE, NOS3, ACE, AGT, and CYP variants influence the therapeutic response to hypotensive drugs in AD patients with hypertension. Consequently, the implementation of pharmacogenetic procedures may optimize therapeutics in AD patients under polypharmacy regimes for the treatment of concomitant vascular disorders.
Open Access
The correlation of two different real-time PCR devices for the analysis of CYP2C19 pharmacogenetic results
(MDPI, 2023) Alonso Llorente, Alba; Salgado Garrido, Josefa; Teijido Hermida, Óscar; González Andrade, Fabricio; Valiente Martín, Alberto; Fanlo Villacampa, Ana; Vicente Romero, Jorge; Ciencias de la Salud; Osasun Zientziak
CYP2C19 is a highly polymorphic gene responsible for the metabolism of commonly used drugs. CYP2C19*1, the wild-type allele, is associated with normal enzyme activity, whereas CYP2C19*2 and CYP2C19*17 lead to null and increased enzyme activity, respectively. The use of different instruments to perform the same pharmacogenetic tests should not affect the reliability of the results reported to clinicians, as required by the ISO 15189 standard. Genotyping assays allowed for the identification of gene variants corresponding to the CYP2C19*2 and CYP2C19*17 haplotypes in 44 selected samples. Each sample was analyzed in duplicate using the Thermo Fisher Taqman Drug Metabolism probes CYP2C19*2: c_25986767_70 (rs4244285) and CYP2C19*17: c_469857_10 (rs12248560). The experiments were performed on two widely used types of real-time PCR analyzers: ABI PRSIM™7500 and QuantStudioTM12KFlex (both from Applied Biosystems, Thermofisher). The data were analyzed in a Thermo Fisher Cloud facility. The analysis was performed independently by two qualified professionals. Both different instruments and analysts’ interpretations were consistent in identifying the native homozygous, heterozygous, and mutant homozygous variants for CYP2C19*2 and CYP2C19*17. The results provided by both the primary and backup analyzers showed a perfect correlation. This would allow for the use of the backup analyzer in case the main one is not available.
Open Access
Genetic polymorphisms of CYP2C19 in Ecuadorian population: an interethnic approach
(Elsevier, 2024) Alonso Llorente, Alba; Salgado Garrido, Josefa; Teijido Hermida, Óscar; González Andrade, Fabricio; Valiente Martín, Alberto; Fanlo Villacampa, Ana; Vicente Romero, Jorge; Ciencias de la Salud; Osasun Zientziak
Introduction: CYP2C19 is a highly polymorphic gene responsible for metabolizing commonly used drugs. CYP2C192,3 (loss of activity alleles) and 17 (increased activity allele) are the principal alleles included in clinical guidelines, however their prevalence varies among different ethnicities. Ecuadorian population is formed by Mestizos, Afrodescendants and Native Americans and frequency of CYP2C19 alleles could be different among them. The objective of this study was to establish the frequency of these variants in the different populations of Ecuador and to compare them with other populations. Materials and methods: DNA from 105 Afrodescendants, 75 Native Americans of the Kichwa ethnicity, and 33 Mestizos Ecuadorians was analyzed by nested-PCR to identify CYP2C1917 carriers. CYP2C192 allele was analyzed in DNA from 78 Afrodescendants, 29 Native Americans of the Kichwa, and 16 Mestizos by TaqMan Allelic Discrimination Assay. CYP2C193 was analyzed in 33 Afrodescendants by nested-PCR. Results: The global frequencies of the alternate alleles were 14.22% (CYP2C192) and 2.10% (CYP2C1917). No differences (p > 0.05) were observed among the subgroups. No CYP2C193 carrier was identified. CYP2C192 frequencies in Ecuador were similar to the ones reported in Europe, Africa and Middle East countries and to some American populations. Low CYP2C1917 frequencies, like the ones in our population, were also observed in East and South Asia and in Native American groups. Discussion: Absence of differences in the ethnic groups in Ecuador for CYP2C192 and 17 could be due to either a bias in sample selection (ethnic group was assed by self-identification) or to a high interethnic admixture in the Ecuadorian population that would had diluted genetic differences. In addition, CYP2C192, *3, and *17 alleles frequencies in our study suggest that Ecuadorians ancestry is mostly of Native American origin.

Teijido Hermida, Óscar

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