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      The Branched-chain Amino Acid Transaminase 1 -23C/G Polymorphism Confers Protection Against Acute Coronary Syndrome

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          Abstract

          ABSTRACT Background: Previous studies have shown an association between polymorphisms of the BAT1-NF-κB inhibitor-like-1 (NFKBIL1)-LTA genomic region and susceptibility to myocardial infarction and acute coronary syndrome (ACS). Objective: The objective of the study was to study the role of three polymorphisms in the BAT1, NFKBIL1, and LTA genes on the susceptibility or protection against ACS; we included a group of cases-controls from Central Mexico. Methods: The BAT1 rs2239527C/G, NFKBIL1 rs2071592T/A, and LTA rs1800683G/A polymorphisms were genotyped using a 5’ TaqMan assay in a group of 625 patients with ACS and 617 healthy controls. Results: Under a recessive model, the BAT1 -23C/G (rs2239527) polymorphism showed an association with protection against ACS (odds ratio = 0.56, and p-corrected = 0.019). In contrast, the genotype and allele frequencies of the NFKBIL1 rs2071592T/A and LTA rs1800683G/A polymorphisms were similar between ACS patients and controls and no association was identified. Conclusion: Our data suggest an association between the BAT1 -23C/G polymorphism and protection against ACS in Mexican patients.

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          Most cited references26

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          Inflammation in atherosclerosis.

          Experimental work has elucidated molecular and cellular pathways of inflammation that promote atherosclerosis. Unraveling the roles of cytokines as inflammatory messengers provided a mechanism whereby risk factors for atherosclerosis can alter arterial biology, and produce a systemic milieu that favors atherothrombotic events. The discovery of the immune basis of allograft arteriosclerosis demonstrated that inflammation per se can drive arterial hyperplasia, even in the absence of traditional risk factors. Inflammation regulates aspects of plaque biology that trigger the thrombotic complications of atherosclerosis. Translation of these discoveries to humans has enabled both novel mechanistic insights and practical clinical advances.
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            Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction.

            By means of a large-scale, case-control association study using 92,788 gene-based single-nucleotide polymorphism (SNP) markers, we identified a candidate locus on chromosome 6p21 associated with susceptibility to myocardial infarction. Subsequent linkage-disequilibrium (LD) mapping and analyses of haplotype structure showed significant associations between myocardial infarction and a single 50 kb halpotype comprised of five SNPs in LTA (encoding lymphotoxin-alpha), NFKBIL1 (encoding nuclear factor of kappa light polypeptide gene enhancer in B cells, inhibitor-like 1) and BAT1 (encoding HLA-B associated transcript 1). Homozygosity with respect to each of the two SNPs in LTA was significantly associated with increased risk for myocardial infarction (odds ratio = 1.78, chi(2) = 21.6, P = 0.00000033; 1,133 affected individuals versus 1,006 controls). In vitro functional analyses indicated that one SNP in the coding region of LTA, which changed an amino-acid residue from threonine to asparagine (Thr26Asn), effected a twofold increase in induction of several cell-adhesion molecules, including VCAM1, in vascular smooth-muscle cells of human coronary artery. Moreover, the SNP, in intron 1 of LTA, enhanced the transcriptional level of LTA. These results indicate that variants in the LTA are risk factors for myocardial infraction and implicate LTA in the pathogenesis of the disorder.
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              ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).

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                Author and article information

                Journal
                ric
                Revista de investigación clínica
                Rev. invest. clín.
                Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (Ciudad de México, Ciudad de México, Mexico )
                0034-8376
                2564-8896
                February 2020
                : 72
                : 1
                : 19-24
                Affiliations
                [4] Mexico City orgnameInstituto Nacional de Cardiología Ignacio Chávez orgdiv1Department of Endocrinology Mexico
                [3] Mexico City orgnameInstituto Nacional de Cardiología Ignacio Chávez orgdiv1Department of Interventional Cardiology Mexico
                [2] Mexico City orgnameInstituto Nacional de Cardiología Ignacio Chávez orgdiv1Department of Molecular Biology Mexico
                [5] Mexico City orgnameHospital Juárez de México orgdiv1Department of Laboratory of Genetics and Molecular Diagnosis Mexico
                [1] Mexico City orgnameHospital Juárez de México orgdiv1Research Unit Mexico
                Article
                S0034-83762020000100019 S0034-8376(20)07200100019
                10.24875/ric.19003133
                32132739
                e6b08243-fa10-4af6-8b17-b3245d70fef1

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 03 June 2019
                : 02 September 2019
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 26, Pages: 6
                Product

                SciELO Mexico

                Categories
                Original articles

                Acute coronary syndrome,BAT,Single-nucleotide polymorphism

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