R46L polymorphism in the PCSK9 gene: Relationship to lipid levels, subclinical vascular disease, and erectile dysfunction

Autor: Concepción Diaz Laso, Froilán Antuña, María Isabel Ferrer Zapata, Pablo Díaz, Alvaro R. Aguirre De Carcer Escolano, M. Jesús Álvarez Otero, Maria Isabel García Lazaro, Begoña Berriatua Ena, María Alejandra Rabanal Carrera, Gerardo López Ruiz Ogarrio, Margarita Ruiz Pacheco, Ana Isabel Bezos Varela, Silvia López, Africa Gómez Lucena, Luis Montesano, Montserrat Nieto Candenas, Sonsoles Paloma Luquero López, Carmen de Burgos, Maria Teresa Gómez Rodríguez, Angel Castellanos Rodríguez, Paloma Arribas Pérez, Belen Fernandez Puntero, Francisca García-Iglesias, Maria Del Carmen Lumbreras Manzano, Francisco Hernandez, Angeles Conde Llorente, Víctor Hugo Cornejo, Maria Luisa. Asensio Ruiz, Orlando Enríquez Dueñas, Ana Martinez Cabrera Pelaez, Carlos Casanova García, Emilia Elviro García, Vanesa Sanchez, María José Calatrava Triguero, Fernando Laguna, Concesa Sabín, Olaya de Dios, Teresa González-Alegre, Patricio Alonso. Sacristán, Pedro J. Fernandez-Garcia, Elisa Castillo, Ana López Castellanos, Concepción Aguilera Linde, Rosa Julián Viñals, Pedro PatronConcepción Aguilera Linde, Milagros García, Carmen Garcés, Carlos Lahoz, Eva Estirado, Miguel A. Salinero-Fort, José M. Mostaza
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Adolescent
Endocrinology
Diabetes and Metabolism
Population
030204 cardiovascular system & hematology
Carotid Intima-Media Thickness
Polymorphism
Single Nucleotide
Gastroenterology
Cohort Studies
Prediabetic State
03 medical and health sciences
0302 clinical medicine
Erectile Dysfunction
Internal medicine
Internal Medicine
medicine
Humans
Vascular Diseases
Allele
Child
education
Alleles
Aged
Apolipoproteins B
Subclinical infection
education.field_of_study
Nutrition and Dietetics
Vascular disease
business.industry
PCSK9
Cholesterol
LDL
Middle Aged
medicine.disease
030104 developmental biology
Erectile dysfunction
Diabetes Mellitus
Type 2
Intima-media thickness
Female
Proprotein Convertase 9
Cardiology and Cardiovascular Medicine
business
Cohort study
Zdroj: Journal of Clinical Lipidology. 12:1039-1046.e3
ISSN: 1933-2874
DOI: 10.1016/j.jacl.2018.04.004
Popis: Background The R46L variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has been related to lipid levels and cardiovascular disease. Objective To evaluate the influence of this polymorphism on subclinical vascular disease and erectile dysfunction (ED). Methods We analyzed the association of the PCSK9 rs11591147 single-nucleotide polymorphism with lipid levels, intima-media thickness (IMT), and the ankle-brachial index, in 1188 adults free of cardiovascular disease, randomly selected from the population. In 473 male participants, we also investigated its relationship with ED. The association of the R46L polymorphism with lipid levels was also assessed in 2 cohorts of 1103 prepuberal children and 830 adolescents. Results The prevalence of the T allele was 2.9% in adults. Low-density lipoprotein cholesterol (LDL-cholesterol) levels did not vary according to this polymorphism (134 ± 32 vs 134 ± 31 mg/dL, for the TT + GT vs GG carriers, respectively, P = .931). Despite equal LDL-cholesterol levels, adults carrying the T allele had a lower mean common carotid IMT (0.685 ± 0.09 vs 0.723 ± 0.127 mm; P = .035), a lower maximum common carotid IMT (0.819 ± 0.11 vs 0.865 ± 0.159 mm; P = .040), and, in males, a lower prevalence of ED (36.8% vs 61%: P = .036), than GG carriers. Prevalence of the T allele was 3.2% in both cohorts of children. They had lower levels of LDL-cholesterol than GG subjects (100 vs 109 mg/dL; P = .060, for prepuberal children, and 85 vs 99 mg/dL; P = .010 for adolescents). Conclusion In our population, an association between the PCSK9 R46L variant and LDL-cholesterol levels is observed in children. In adults, although its association with lipid levels is not evident, there is a significant relationship between the PCSK9 R46L variant and markers of subclinical atherosclerosis, including IMT and ED.
Databáze: OpenAIRE
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