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Metabolic Overlap between Alzheimer’s Disease and Metabolic Syndrome Identifies the PVRL2 Gene as a New Modulator of Diabetic Dyslipidemia

  • Identification data

    Identifier: imarina:9295851
  • Authors:

    Guardiola, M
    Muntané, G
    Martínez, I
    Martorell, L
    Girona, J
    Ibarretxe, D
    Plana, N
    Bullido, MJ
    Vilella, E
    Ribalta, J
  • Others:

    Author, as appears in the article.: Guardiola, M; Muntané, G; Martínez, I; Martorell, L; Girona, J; Ibarretxe, D; Plana, N; Bullido, MJ; Vilella, E; Ribalta, J
    Department: Ciències Mèdiques Bàsiques Medicina i Cirurgia
    URV's Author/s: Alkhoury, Nadine / Girona Tell, Josefa / Guardiola Guionnet, Montserrat / Ibarretxe Gerediaga, Daiana / Martorell Bonet, Lourdes / Muntané Medina, Gerard / Plana Gil, Núria / Ribalta Vives, Josep / Vilella Cuadrada, Elisabet
    Keywords: Pvrl2 Low-density-lipoprotein Lipid Diabetes Alzheimer’s disease Alzheimer's disease risk-factor pvrl2 polymorphism oxidative stress mechanisms lipid impairment diabetes dementia cholesterol atherosclerosis association
    Abstract: Background: Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) share metabolic alterations such as abnormal insulin and lipid metabolism and have some common genetic factors such as APOE genotype. Taking this into account, we hypothesized that we could identify common genetic factors involved in the development of diabetes and cardiovascular diseases. Methodology: We first genotyped 48 single nucleotide polymorphisms (SNPs) previously associated with AD in a cohort composed of 330 patients with cognitive impairment (CI) to assess their association with plasma lipids. Second, we conducted pleiotropy-informed conjunctional false discovery rate (FDR) analysis designed to identify shared variants between AD and plasma lipid levels. Finally, we used the SNPs to be found associated with lipid parameters and AD to search for associations with lipoprotein parameters in 281 patients with cardiometabolic risk. Results: Five SNPs were significantly associated with lower levels of cholesterol transported in remnant lipoprotein particles (RLPc) in subjects with CI; among these SNPs was the rs73572039 variant in PVRL2. Stratified QQ-plots were conducted on GWAS designed for AD and triglycerides (TG). The cross-trait analysis resulted in a total of 22 independent genomic loci associated with both AD and TG levels with a conjFDR < 0.05. Among these loci, two pleiotropic variants were located in PVRL2 (rs12978931 and rs11667640). The three SNPs in PVRL2 were significantly associated with RLPc, TG, and number of circulating VLDL and HDL particles in subjects with cardiometabolic risk. Conclusions: We have identified three variants in PVRL2 that predispose individuals to AD that also influence the lipid profile that confers cardiovascular risk in T2DM subjects. PVRL2 is a potential new modulating factor of atherogenic dyslipidemia.
    Thematic Areas: Zootecnia / recursos pesqueiros Spectroscopy Saúde coletiva Química Psicología Physical and theoretical chemistry Organic chemistry Odontología Nutrição Molecular biology Medicine (miscellaneous) Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Interdisciplinar Inorganic chemistry Geociências Farmacia Engenharias iv Engenharias ii Engenharias i Educação física Computer science applications Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência de alimentos Ciência da computação Chemistry, multidisciplinary Catalysis Biotecnología Biodiversidade Biochemistry & molecular biology Astronomia / física
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: gerard.muntane@urv.cat daiana.ibarretxe@urv.cat josefa.girona@urv.cat lourdes.martorell@urv.cat elisabet.vilella@urv.cat josep.ribalta@urv.cat montse.guardiola@urv.cat josefa.girona@urv.cat nadine.alkhoury@estudiants.urv.cat nadine.alkhoury@estudiants.urv.cat nadine.alkhoury@estudiants.urv.cat nadine.alkhoury@estudiants.urv.cat
    Author identifier: 0000-0002-6267-8779 0000-0003-4999-2197 0000-0002-1887-5919 0000-0002-8879-4719 0000-0002-9696-7384 0000-0002-6267-8779
    Record's date: 2024-01-13
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://www.mdpi.com/1422-0067/24/8/7415
    Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: International Journal Of Molecular Sciences. 24 (8): 7415-
    APA: Guardiola, M; Muntané, G; Martínez, I; Martorell, L; Girona, J; Ibarretxe, D; Plana, N; Bullido, MJ; Vilella, E; Ribalta, J (2023). Metabolic Overlap between Alzheimer’s Disease and Metabolic Syndrome Identifies the PVRL2 Gene as a New Modulator of Diabetic Dyslipidemia. International Journal Of Molecular Sciences, 24(8), 7415-. DOI: 10.3390/ijms24087415
    Article's DOI: 10.3390/ijms24087415
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2023
    Publication Type: Journal Publications
  • Keywords:

    Biochemistry & Molecular Biology,Catalysis,Chemistry, Multidisciplinary,Computer Science Applications,Inorganic Chemistry,Medicine (Miscellaneous),Molecular Biology,Organic Chemistry,Physical and Theoretical Chemistry,Spectroscopy
    Pvrl2
    Low-density-lipoprotein
    Lipid
    Diabetes
    Alzheimer’s disease
    Alzheimer's disease
    risk-factor
    pvrl2
    polymorphism
    oxidative stress
    mechanisms
    lipid
    impairment
    diabetes
    dementia
    cholesterol
    atherosclerosis
    association
    Zootecnia / recursos pesqueiros
    Spectroscopy
    Saúde coletiva
    Química
    Psicología
    Physical and theoretical chemistry
    Organic chemistry
    Odontología
    Nutrição
    Molecular biology
    Medicine (miscellaneous)
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Materiais
    Interdisciplinar
    Inorganic chemistry
    Geociências
    Farmacia
    Engenharias iv
    Engenharias ii
    Engenharias i
    Educação física
    Computer science applications
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências ambientais
    Ciências agrárias i
    Ciência de alimentos
    Ciência da computação
    Chemistry, multidisciplinary
    Catalysis
    Biotecnología
    Biodiversidade
    Biochemistry & molecular biology
    Astronomia / física
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