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: daiana.ibarretxe@urv.cat gerard.muntane@urv.cat josefa.girona@urv.cat lourdes.martorell@urv.cat elisabet.vilella@urv.cat nadine.alkhoury@estudiants.urv.cat nadine.alkhoury@estudiants.urv.cat nadine.alkhoury@estudiants.urv.cat nadine.alkhoury@estudiants.urv.cat josefa.girona@urv.cat montse.guardiola@urv.cat josep.ribalta@urv.cat
Author identifier: 0000-0002-6267-8779 0000-0003-4999-2197 0000-0002-1887-5919 0000-0002-6267-8779 0000-0002-9696-7384 0000-0002-8879-4719
Record's date: 2024-08-03
Papper version: info:eu-repo/semantics/publishedVersion
Licence document URL: https://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
Entity: Universitat Rovira i Virgili
Journal publication year: 2023
Publication Type: Journal Publications
Repositori URV