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  1. Article ; Online: Genetic Determinants of Atherogenic Indexes

    Texis, Tomas / Rivera-Mancía, Susana / Colín, Eloísa / Cartas-Rosado, Raul / Koepsell, David / Rubio-Carrasco, Kenneth / Rodríguez-Dorantes, Mauricio / Gonzalez-Covarrubias, Vanessa

    Genes (Basel). 2023 June 01, v. 14, no. 6

    2023  

    Abstract: Atherogenesis and dyslipidemia increase the risk of cardiovascular disease, which is the leading cause of death in developed countries. While blood lipid levels have been studied as disease predictors, their accuracy in predicting cardiovascular risk is ... ...

    Abstract Atherogenesis and dyslipidemia increase the risk of cardiovascular disease, which is the leading cause of death in developed countries. While blood lipid levels have been studied as disease predictors, their accuracy in predicting cardiovascular risk is limited due to their high interindividual and interpopulation variability. The lipid ratios, atherogenic index of plasma (AIP = log TG/HDL-C) and the Castelli risk index 2 (CI2 = LDL-C/HDL-C), have been proposed as better predictors of cardiovascular risk, but the genetic variability associated with these ratios has not been investigated. This study aimed to identify genetic associations with these indexes. The study population (n = 426) included males (40%) and females (60%) aged 18–52 years (mean 39 years); the Infinium GSA array was used for genotyping. Regression models were developed using R and PLINK. AIP was associated with variation on APOC3, KCND3, CYBA, CCDC141/TTN, and ARRB1 (p-value < 2.1 × 10⁻⁶). The three former were previously associated with blood lipids, while CI2 was associated with variants on DIPK2B, LIPC, and 10q21.3 rs11251177 (p-value 1.1 × 10⁻⁷). The latter was previously linked to coronary atherosclerosis and hypertension. KCND3 rs6703437 was associated with both indexes. This study is the first to characterize the potential link between genetic variation and atherogenic indexes, AIP, and CI2, highlighting the relationship between genetic variation and dyslipidemia predictors. These results also contribute to consolidating the genetics of blood lipid and lipid indexes.
    Keywords atherogenesis ; blood ; blood lipids ; coronary artery disease ; death ; genetic variation ; genotyping ; hyperlipidemia ; hypertension ; lipids ; risk
    Language English
    Dates of publication 2023-0601
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article ; Online
    ZDB-ID 2527218-4
    ISSN 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes14061214
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: Genetic Determinants of Atherogenic Indexes.

    Texis, Tomas / Rivera-Mancía, Susana / Colín-Ramírez, Eloisa / Cartas-Rosado, Raul / Koepsell, David / Rubio-Carrasco, Kenneth / Rodríguez-Dorantes, Mauricio / Gonzalez-Covarrubias, Vanessa

    Genes

    2023  Volume 14, Issue 6

    Abstract: Atherogenesis and dyslipidemia increase the risk of cardiovascular disease, which is the leading cause of death in developed countries. While blood lipid levels have been studied as disease predictors, their accuracy in predicting cardiovascular risk is ... ...

    Abstract Atherogenesis and dyslipidemia increase the risk of cardiovascular disease, which is the leading cause of death in developed countries. While blood lipid levels have been studied as disease predictors, their accuracy in predicting cardiovascular risk is limited due to their high interindividual and interpopulation variability. The lipid ratios, atherogenic index of plasma (AIP = log TG/HDL-C) and the Castelli risk index 2 (CI2 = LDL-C/HDL-C), have been proposed as better predictors of cardiovascular risk, but the genetic variability associated with these ratios has not been investigated. This study aimed to identify genetic associations with these indexes. The study population (n = 426) included males (40%) and females (60%) aged 18-52 years (mean 39 years); the Infinium GSA array was used for genotyping. Regression models were developed using R and PLINK. AIP was associated with variation on
    MeSH term(s) Male ; Female ; Humans ; Case-Control Studies ; Atherosclerosis/genetics ; Coronary Artery Disease/genetics ; Lipids ; Dyslipidemias/genetics
    Chemical Substances Lipids
    Language English
    Publishing date 2023-06-01
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2527218-4
    ISSN 2073-4425 ; 2073-4425
    ISSN (online) 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes14061214
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Ball-Milling Preparation of the Drug-Drug Solid Form of Pioglitazone-Rosuvastatin at Different Molar Ratios: Characterization and Intrinsic Dissolution Rates Evaluation.

    Muñoz Tecocoatzi, M Fernanda / Páez-Franco, José C / Rubio-Carrasco, Kenneth / Núñez-Pineda, Alejandra / Dorazco-González, Alejandro / Fuentes-Noriega, Inés / Vilchis-Néstor, Alfredo R / Olvera, Lilian I / Morales-Morales, David / Germán-Acacio, Juan Manuel

    Pharmaceutics

    2023  Volume 15, Issue 2

    Abstract: Ball-milling using neat grinding (NG) or liquid-assisted grinding (LAG) by varying the polarity of the solvents allowed access to various drug-drug solid forms of pioglitazone hydrochloride (PGZ·HCl) and rosuvastatin calcium (RSV). Using NG, the ... ...

    Abstract Ball-milling using neat grinding (NG) or liquid-assisted grinding (LAG) by varying the polarity of the solvents allowed access to various drug-drug solid forms of pioglitazone hydrochloride (PGZ·HCl) and rosuvastatin calcium (RSV). Using NG, the coamorphous form was formed from the reaction of pioglitazone hydrochloride (PGZ·HCl) and rosuvastatin calcium (RSV) in a 2:1 molar ratio. The formation of the expected coamorphous salt could not be corroborated by FT-IR, but DSC data showed that it was indeed a single-phase amorphous mixture. By varying the molar ratios of the reactants, either keeping PGZ·HCl constant and varying RSV or vice versa, another coamorphous form was obtained when a 1:1 molar ratio was employed. In the case of the other outcomes, it was observed that they were a mixture of solid forms coexisting simultaneously with the coamorphous forms (1:1 or 2:1) together with the drug that was in excess. When RSV was in excess, it was in an amorphous form. In the case of PGZ·HCl, it was found in a semicrystalline form. The intrinsic dissolution rates (IDRs) of the solid forms of PGZ·HCl-RSV in stoichiometric ratios (1:1, 2:1, 1:4, 6:1, and 1:10) were evaluated. Interestingly, a synchronized release of both drugs in the dissolution medium was observed. In the case of the release of RSV, there were no improvements in the dissolution profiles, because the acidic media caused the formation of degradation products, limiting any probable modification in the dissolution processes. However, the coamorphous 2:1 form exhibited an improvement of 1.03 times with respect to pure PGZ·HCl. It is proposed that the modification of the dissolution process of the coamorphous 2:1 form was limited by changes in the pH of the media as RSV consumes protons from the media due to degradation processes.
    Language English
    Publishing date 2023-02-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics15020630
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Diversity of Solid Forms Promoted by Ball Milling: Characterization and Intrinsic Dissolution Studies of Pioglitazone Hydrochloride and Fluvastatin Sodium Drug-Drug Systems.

    Villeda-Villegas, Marco / Páez-Franco, José C / Coyote-Dotor, Guadalupe / Núñez-Pineda, Alejandra / Dorazco-González, Alejandro / Fuentes-Noriega, Inés / Rubio-Carrasco, Kenneth / Toledo Jaldín, Helen P / Morales-Morales, David / Germán-Acacio, Juan Manuel

    Pharmaceuticals (Basel, Switzerland)

    2023  Volume 16, Issue 6

    Abstract: Coamorphous salt in a 1:1 ratio prepared by ball milling from Fluvastatin sodium (FLV) and Pioglitazone hydrochloride (PGZ·HCl) can be selectively formed by neat grinding (NG). Furthermore, the salt-cocrystal continuum was preferably formed by employing ... ...

    Abstract Coamorphous salt in a 1:1 ratio prepared by ball milling from Fluvastatin sodium (FLV) and Pioglitazone hydrochloride (PGZ·HCl) can be selectively formed by neat grinding (NG). Furthermore, the salt-cocrystal continuum was preferably formed by employing liquid-assisted grinding (LAG) using ethanol (EtOH). Attempts to prepare the coamorphous salt starting from the salt-cocrystal continuum by NG were unsuccessful. Interestingly, through ball milling by NG or LAG, a great diversity of solid forms (PGZ·HCl-FLV 1:1) could be accessed: NG and hexane (coamorphous); ethyl acetate (physical mixture); EtOH (salt-cocrystal continuum); and water (which presents two T
    Language English
    Publishing date 2023-05-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph16060781
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Pharmacogenomics: Current Actionable Variants.

    González-Covarrubias, Vanessa / Lozano, Karla / Texis, Tomas / Guzmán-Cruz, Cintia K / Rodríguez-Dorantes, Mauricio / Rubio-Carrasco, Kenneth / Méndez-Lorenzo, Luz H / Soberón, Xavier

    Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion

    2020  Volume 73, Issue 3

    Abstract: Pharmacogenomics (PGx), one of the several tools of precision medicine, has been slowly implemented in the clinic during the past decades. This process generally starts with direct and indirect genotype-phenotype associations of gene variants and drug ... ...

    Abstract Pharmacogenomics (PGx), one of the several tools of precision medicine, has been slowly implemented in the clinic during the past decades. This process generally starts with direct and indirect genotype-phenotype associations of gene variants and drug efficacy, or adverse drug reactions, followed by replication and validation studies. Institutional efforts led by the PGx Research Network, The PGx Knowledge Base, and The Clinical Pharmacogenetics Implementation Consortium, mine all available data for further validation or research in additional populations. This data mining gives rise to a detailed classification of over 200 druggene pairs which, with enough documentation, may become part of a publishable guideline to aid clinicians in drug selection and dosing using genetics. The US Food and Drug Administration utilizes these guidelines to issue warnings and recommendations for specific drugs and their cautioning serves clinicians and pharmacists worldwide. Here, we aim to discuss the steps of this process and list existing actionable drug-gene pairs. Moreover, we describe the current status of PGx knowledge in populations from Mexico for actionable variants on the 19 genes listed by present PGx guidelines affecting 47 drugs. Our review collects current allele frequency information for these actionable variants, lists gaps of PGx information for relevant markers, and highlights the importance of continuing PGx research in Native and Mestizo populations.
    Language English
    Publishing date 2020-05-07
    Publishing country Mexico
    Document type Journal Article
    ZDB-ID 138348-6
    ISSN 0034-8376
    ISSN 0034-8376
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: COVID-19 relevant genetic variants confirmed in an admixed population

    Texis, Tomas / Cruz-Jaramilllo, Jose Luis / Garcia-Munoz, Willebaldo / Anzures-Cortes, Lourdes / Hadadd-Talancon, Lorenza / Sanchez-Garcia, Sergio / Jimenez-Martinez, Maria del Carmen / Perez-Barragan, Edgar / Nieto-Patlan, Alejandro / Martinez-Ezquerro, Jose Dario / Rubio-Carrasco, Kenneth / Rodriguez-Dorantes, Mauricio / Cortes-Ramirez, Sergio / Mellado-Sanchez, Gabriela / Perez-Tapia, Sonia Mayra / Gonzalez-Covarrubias, Vanessa

    medRxiv

    Abstract: The dissection of factors that contribute to COVID-19 infection and severity has overwhelmed the scientific community for almost 2 years. Current reports highlight the role of in disease incidence, progression, and severity. Here, we aimed to confirm the ...

    Abstract The dissection of factors that contribute to COVID-19 infection and severity has overwhelmed the scientific community for almost 2 years. Current reports highlight the role of in disease incidence, progression, and severity. Here, we aimed to confirm the presence of previously reported genetic variants in an admixed population. Allele frequencies were assessed and compared between the general population (N=3079) for which at least 30% have not been infected with SARS-CoV2 as per July 2021 versus COVID-19 patients (N=106). Genotyping data from the Illumina GSA array was used to impute genetic variation for 14 COVID-relevant genes, using the 1000G phase 3 as reference based on the human genome assembly hg19, following current standard protocols and recommendations for genetic imputation. Bioinformatic and statistical analyses were performed using MACH v1.0, R, and PLINK. A total of 7953 variants were imputed on, ABO, CCR2, CCR9, CXCR6, DPP9, FYCO1, IL10RB/IFNAR2, LZTFL1, OAS1, OAS2, OAS3, SLC6A20, TYK2, and XCR1. Statistically significant allele differences were reported for 10 and 7 previously identified and confirmed variants, ABO rs657152, DPP9 rs2109069, LZTFL1 rs11385942, OAS1 rs10774671, OAS1 rs2660, OAS2 rs1293767, and OAS3 rs1859330 p<0.03. In addition, we identified 842 variants in these COVID-related genes with significant allele frequency differences between COVID patients and the general population (p-value <E-2 to E-179). Our observations confirm the presence of genetic differences in COVID-19 patients in an admixed population and prompts for the investigation of the statistical relevance of additional variants on these and other genes that could identify local and geographical patterns of COVID-19.<br />
    Keywords covid19
    Language English
    Publishing date 2022-04-16
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2022.04.15.22273925
    Database COVID19

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