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Single Nucleotide Polymorphisms within LIPA (Lysosomal Acid Lipase A) Gene Are Associated with Susceptibility to Premature Coronary Artery Disease. A Replication in the Genetic of Atherosclerotic Disease (GEA) Mexican Study
AIM: The rs1412444 and rs2246833 polymorphisms within the LIPA gene were recently found to be significantly associated with coronary artery disease (CAD) in genome-wide association studies in Caucasian and Asian populations. The aim of the present study was to replicate this association in an indepe...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775807/ https://www.ncbi.nlm.nih.gov/pubmed/24069331 http://dx.doi.org/10.1371/journal.pone.0074703 |
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author | Vargas-Alarcón, Gilberto Posadas-Romero, Carlos Villarreal-Molina, Teresa Alvarez-León, Edith Angeles, Javier Vallejo, Maite Posadas-Sánchez, Rosalinda Cardoso, Guillermo Medina-Urrutia, Aida Kimura-Hayama, Eric |
author_facet | Vargas-Alarcón, Gilberto Posadas-Romero, Carlos Villarreal-Molina, Teresa Alvarez-León, Edith Angeles, Javier Vallejo, Maite Posadas-Sánchez, Rosalinda Cardoso, Guillermo Medina-Urrutia, Aida Kimura-Hayama, Eric |
author_sort | Vargas-Alarcón, Gilberto |
collection | PubMed |
description | AIM: The rs1412444 and rs2246833 polymorphisms within the LIPA gene were recently found to be significantly associated with coronary artery disease (CAD) in genome-wide association studies in Caucasian and Asian populations. The aim of the present study was to replicate this association in an independent population with a different genetic background. METHODS: The rs1412444 and rs2246833 polymorphisms of the LIPA gene were genotyped by 5′ exonuclease TaqMan genotyping assays in a sample of 899 Mexican patients with premature CAD, 270 individuals with subclinical atherosclerosis, and 677 healthy unrelated controls. Haplotypes were constructed after linkage disequilibrium analysis. RESULTS: Under recessive and additive models, the rs1412444 T and rs2246833 T alleles were associated with an increased risk of premature CAD when compared to controls adjusting for age, gender, BMI, and total cholesterol (OR = 1.53, P(Rec) = 0.0013 and OR = 1.34, P(Add) = 5 × 10(-4) for rs1412444 and OR = 1.45, P(Rec) = 0.0039 and OR = 1.28, P(Add) = 0.0023 for rs2246833). The effect of the two polymorphisms on various metabolic cardiovascular risk factors was analyzed in premature CAD and controls (CAC score = 0). The T alleles in both polymorphisms after adjusting for age, gender, BMI, and medication were associated with hypo-α-lipoproteinemia, hypercholesterolemia, hypertriglyceridemia, metabolic syndrome, and type 2 diabetes mellitus using recessive and additive models. The polymorphisms were in strong linkage disequilibrium and, based on SNP functional prediction software, only the rs1412444 polymorphism seemed to be functional. CONCLUSIONS: These results indicate that the rs1412444 and rs2246833 of the LIPA gene are shared susceptibility polymorphisms for CAD among different ethnicities. |
format | Online Article Text |
id | pubmed-3775807 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37758072013-09-25 Single Nucleotide Polymorphisms within LIPA (Lysosomal Acid Lipase A) Gene Are Associated with Susceptibility to Premature Coronary Artery Disease. A Replication in the Genetic of Atherosclerotic Disease (GEA) Mexican Study Vargas-Alarcón, Gilberto Posadas-Romero, Carlos Villarreal-Molina, Teresa Alvarez-León, Edith Angeles, Javier Vallejo, Maite Posadas-Sánchez, Rosalinda Cardoso, Guillermo Medina-Urrutia, Aida Kimura-Hayama, Eric PLoS One Research Article AIM: The rs1412444 and rs2246833 polymorphisms within the LIPA gene were recently found to be significantly associated with coronary artery disease (CAD) in genome-wide association studies in Caucasian and Asian populations. The aim of the present study was to replicate this association in an independent population with a different genetic background. METHODS: The rs1412444 and rs2246833 polymorphisms of the LIPA gene were genotyped by 5′ exonuclease TaqMan genotyping assays in a sample of 899 Mexican patients with premature CAD, 270 individuals with subclinical atherosclerosis, and 677 healthy unrelated controls. Haplotypes were constructed after linkage disequilibrium analysis. RESULTS: Under recessive and additive models, the rs1412444 T and rs2246833 T alleles were associated with an increased risk of premature CAD when compared to controls adjusting for age, gender, BMI, and total cholesterol (OR = 1.53, P(Rec) = 0.0013 and OR = 1.34, P(Add) = 5 × 10(-4) for rs1412444 and OR = 1.45, P(Rec) = 0.0039 and OR = 1.28, P(Add) = 0.0023 for rs2246833). The effect of the two polymorphisms on various metabolic cardiovascular risk factors was analyzed in premature CAD and controls (CAC score = 0). The T alleles in both polymorphisms after adjusting for age, gender, BMI, and medication were associated with hypo-α-lipoproteinemia, hypercholesterolemia, hypertriglyceridemia, metabolic syndrome, and type 2 diabetes mellitus using recessive and additive models. The polymorphisms were in strong linkage disequilibrium and, based on SNP functional prediction software, only the rs1412444 polymorphism seemed to be functional. CONCLUSIONS: These results indicate that the rs1412444 and rs2246833 of the LIPA gene are shared susceptibility polymorphisms for CAD among different ethnicities. Public Library of Science 2013-09-17 /pmc/articles/PMC3775807/ /pubmed/24069331 http://dx.doi.org/10.1371/journal.pone.0074703 Text en © 2013 Vargas-Alarcón et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Vargas-Alarcón, Gilberto Posadas-Romero, Carlos Villarreal-Molina, Teresa Alvarez-León, Edith Angeles, Javier Vallejo, Maite Posadas-Sánchez, Rosalinda Cardoso, Guillermo Medina-Urrutia, Aida Kimura-Hayama, Eric Single Nucleotide Polymorphisms within LIPA (Lysosomal Acid Lipase A) Gene Are Associated with Susceptibility to Premature Coronary Artery Disease. A Replication in the Genetic of Atherosclerotic Disease (GEA) Mexican Study |
title | Single Nucleotide Polymorphisms within LIPA (Lysosomal Acid Lipase A) Gene Are Associated with Susceptibility to Premature Coronary Artery Disease. A Replication in the Genetic of Atherosclerotic Disease (GEA) Mexican Study |
title_full | Single Nucleotide Polymorphisms within LIPA (Lysosomal Acid Lipase A) Gene Are Associated with Susceptibility to Premature Coronary Artery Disease. A Replication in the Genetic of Atherosclerotic Disease (GEA) Mexican Study |
title_fullStr | Single Nucleotide Polymorphisms within LIPA (Lysosomal Acid Lipase A) Gene Are Associated with Susceptibility to Premature Coronary Artery Disease. A Replication in the Genetic of Atherosclerotic Disease (GEA) Mexican Study |
title_full_unstemmed | Single Nucleotide Polymorphisms within LIPA (Lysosomal Acid Lipase A) Gene Are Associated with Susceptibility to Premature Coronary Artery Disease. A Replication in the Genetic of Atherosclerotic Disease (GEA) Mexican Study |
title_short | Single Nucleotide Polymorphisms within LIPA (Lysosomal Acid Lipase A) Gene Are Associated with Susceptibility to Premature Coronary Artery Disease. A Replication in the Genetic of Atherosclerotic Disease (GEA) Mexican Study |
title_sort | single nucleotide polymorphisms within lipa (lysosomal acid lipase a) gene are associated with susceptibility to premature coronary artery disease. a replication in the genetic of atherosclerotic disease (gea) mexican study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775807/ https://www.ncbi.nlm.nih.gov/pubmed/24069331 http://dx.doi.org/10.1371/journal.pone.0074703 |
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