A study of the role of GATA4 polymorphism in cardiovascular metabolic disorders
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PRIMARY RESEARCH
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A study of the role of GATA4 polymorphism in cardiovascular metabolic disorders Nzioka P Muiya, Salma M Wakil, Asma I Tahir, Samya Hagos, Mohammed Najai, Daisy Gueco, Nada Al-Tassan, Editha Andres, Nejat Mazher, Brian F Meyer and Nduna Dzimiri*
Abstract 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 (χ2 = 4.71; p = 0.041) and GACCCGTG (χ2 = 3.84; p = 0.050) constructed from the SNPs were associated with CAD and ACCCACGC (χ2 = 6.58; p = 0.010) with myocardial infarction, while hypercholesterolaemia (χ2 = 3.86; p = 0.050) and hLDLC (χ2 = 4.94; p = 0.026) shared the AACCCATGT, and AACCCATGTC was associated with hLDLC (χ2 = 4.83; p = 0.028). A 10-mer GACCCGCGCC (χ2 = 7.59; p = 0.006) was associated with obesity (1,631 vs 2,362), and the GACACACCC (χ2 = 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. Keywords: GATA4 gene polymorphism, Haplotypes, Coronary artery disease, Dyslipidaemia, High-density lipoprotein-cholesterol, Hypercholesterolaemia, Hypertriglyceridaemia, Low-density lipoprotein-cholesterol
Background The GATA binding proteins constitute a family of cellrestricted zinc-finger transcription factors (TFs), which recognize the GATA motif present in the promoters of many genes. This family, comprising six developmental/ cell-type specific transcription factors, GATA1-6, is critical to the development of diverse tissues [1-4] and acts in cooperation with more widely expressed factors to direct lineage-specific gene expression [5-11]. Their
* Correspondence: [email protected] Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, S
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