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A study of the role of GATA4 polymorphism in cardiovascular metabolic disorders

BACKGROUND: The study was designed to evaluate the association of GATA4 gene polymorphism with coronary artery disease (CAD) and its metabolic risk factors, including dyslipidaemic disorders, obesity, type 2 diabetes and hypertension, following a preliminary study linking early onset of CAD in heter...

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Autores principales: Muiya, Nzioka P, Wakil, Salma M, Tahir, Asma I, Hagos, Samya, Najai, Mohammed, Gueco, Daisy, Al-Tassan, Nada, Andres, Editha, Mazher, Nejat, Meyer, Brian F, Dzimiri, Nduna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899629/
https://www.ncbi.nlm.nih.gov/pubmed/24330461
http://dx.doi.org/10.1186/1479-7364-7-25
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author Muiya, Nzioka P
Wakil, Salma M
Tahir, Asma I
Hagos, Samya
Najai, Mohammed
Gueco, Daisy
Al-Tassan, Nada
Andres, Editha
Mazher, Nejat
Meyer, Brian F
Dzimiri, Nduna
author_facet Muiya, Nzioka P
Wakil, Salma M
Tahir, Asma I
Hagos, Samya
Najai, Mohammed
Gueco, Daisy
Al-Tassan, Nada
Andres, Editha
Mazher, Nejat
Meyer, Brian F
Dzimiri, Nduna
author_sort Muiya, Nzioka P
collection PubMed
description BACKGROUND: The study was designed to evaluate the association of GATA4 gene polymorphism with coronary artery disease (CAD) and its metabolic risk factors, including dyslipidaemic disorders, obesity, type 2 diabetes and hypertension, following a preliminary study linking early onset of CAD in heterozygous familial hypercholesterolaemia to chromosome 8, which harbours the GATA4 gene. RESULTS: We first sequenced the whole GATA4 gene in 250 individuals to identify variants of interest and then investigated the association of 12 single-nucleotide polymorphisms (SNPs) with the disease traits using Taqman chemistry in 4,278 angiographed Saudi individuals. Of the studied SNPs, rs804280 (1.14 (1.03 to 1.27); p = 0.009) was associated with CAD (2,274 cases vs 2,004 controls), hypercholesterolaemia (1,590 vs 2,487) (1.61 (1.03–2.52); p = 0.037) and elevated low-density lipoprotein-cholesterol (hLDLC) (575 vs 3,404) (1.87 (1.10–3.15); p = 0.020). Additionally, rs3729855_T (1.52 (1.09–2.11; p = 0.013)) and rs17153743 (AG + GG) (2.30 (1.30–4.26); p = 0.005) were implicated in hypertension (3,312 vs 966), following adjustments for confounders. Furthermore, haplotypes CCCGTGCC (χ(2) = 4.71; p = 0.041) and GACCCGTG (χ(2) = 3.84; p = 0.050) constructed from the SNPs were associated with CAD and ACCCACGC (χ(2) = 6.58; p = 0.010) with myocardial infarction, while hypercholesterolaemia (χ(2) = 3.86; p = 0.050) and hLDLC (χ(2) = 4.94; p = 0.026) shared the AACCCATGT, and AACCCATGTC was associated with hLDLC (χ(2) = 4.83; p = 0.028). A 10-mer GACCCGCGCC (χ(2) = 7.59; p = 0.006) was associated with obesity (1,631 vs 2,362), and the GACACACCC (χ(2) = 4.05; p = 0.044) was implicated in type 2 diabetes mellitus 2,378 vs 1,900). CONCLUSION: Our study implicates GATA4 in CAD and its metabolic risk traits. The finding also points to the possible involvement of yet undefined entities related to GATA4 transcription activity or gene regulatory pathways in events leading to these cardiovascular disorders.
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spelling pubmed-38996292014-02-06 A study of the role of GATA4 polymorphism in cardiovascular metabolic disorders Muiya, Nzioka P Wakil, Salma M Tahir, Asma I Hagos, Samya Najai, Mohammed Gueco, Daisy Al-Tassan, Nada Andres, Editha Mazher, Nejat Meyer, Brian F Dzimiri, Nduna Hum Genomics Primary Research BACKGROUND: The study was designed to evaluate the association of GATA4 gene polymorphism with coronary artery disease (CAD) and its metabolic risk factors, including dyslipidaemic disorders, obesity, type 2 diabetes and hypertension, following a preliminary study linking early onset of CAD in heterozygous familial hypercholesterolaemia to chromosome 8, which harbours the GATA4 gene. RESULTS: We first sequenced the whole GATA4 gene in 250 individuals to identify variants of interest and then investigated the association of 12 single-nucleotide polymorphisms (SNPs) with the disease traits using Taqman chemistry in 4,278 angiographed Saudi individuals. Of the studied SNPs, rs804280 (1.14 (1.03 to 1.27); p = 0.009) was associated with CAD (2,274 cases vs 2,004 controls), hypercholesterolaemia (1,590 vs 2,487) (1.61 (1.03–2.52); p = 0.037) and elevated low-density lipoprotein-cholesterol (hLDLC) (575 vs 3,404) (1.87 (1.10–3.15); p = 0.020). Additionally, rs3729855_T (1.52 (1.09–2.11; p = 0.013)) and rs17153743 (AG + GG) (2.30 (1.30–4.26); p = 0.005) were implicated in hypertension (3,312 vs 966), following adjustments for confounders. Furthermore, haplotypes CCCGTGCC (χ(2) = 4.71; p = 0.041) and GACCCGTG (χ(2) = 3.84; p = 0.050) constructed from the SNPs were associated with CAD and ACCCACGC (χ(2) = 6.58; p = 0.010) with myocardial infarction, while hypercholesterolaemia (χ(2) = 3.86; p = 0.050) and hLDLC (χ(2) = 4.94; p = 0.026) shared the AACCCATGT, and AACCCATGTC was associated with hLDLC (χ(2) = 4.83; p = 0.028). A 10-mer GACCCGCGCC (χ(2) = 7.59; p = 0.006) was associated with obesity (1,631 vs 2,362), and the GACACACCC (χ(2) = 4.05; p = 0.044) was implicated in type 2 diabetes mellitus 2,378 vs 1,900). CONCLUSION: Our study implicates GATA4 in CAD and its metabolic risk traits. The finding also points to the possible involvement of yet undefined entities related to GATA4 transcription activity or gene regulatory pathways in events leading to these cardiovascular disorders. BioMed Central 2013-12-12 /pmc/articles/PMC3899629/ /pubmed/24330461 http://dx.doi.org/10.1186/1479-7364-7-25 Text en Copyright © 2013 Muiya et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Primary Research
Muiya, Nzioka P
Wakil, Salma M
Tahir, Asma I
Hagos, Samya
Najai, Mohammed
Gueco, Daisy
Al-Tassan, Nada
Andres, Editha
Mazher, Nejat
Meyer, Brian F
Dzimiri, Nduna
A study of the role of GATA4 polymorphism in cardiovascular metabolic disorders
title A study of the role of GATA4 polymorphism in cardiovascular metabolic disorders
title_full A study of the role of GATA4 polymorphism in cardiovascular metabolic disorders
title_fullStr A study of the role of GATA4 polymorphism in cardiovascular metabolic disorders
title_full_unstemmed A study of the role of GATA4 polymorphism in cardiovascular metabolic disorders
title_short A study of the role of GATA4 polymorphism in cardiovascular metabolic disorders
title_sort study of the role of gata4 polymorphism in cardiovascular metabolic disorders
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899629/
https://www.ncbi.nlm.nih.gov/pubmed/24330461
http://dx.doi.org/10.1186/1479-7364-7-25
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