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

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.

CASP1 Gene Polymorphisms and BAT1-NFKBIL-LTA-CASP1 Gene–Gene Interactions Are Associated with Restenosis after Coronary Stenting

“…Recent studies have shown that the polymorphisms ( BAT1 rs2239527 C / G , NFKBIL1 rs2071592 T / A , LTA rs1800683 G / A , CASP1 rs501192 A / G , and CASP1 rs580253 A / G ) are associated with the presence of ACS, myocardial infarction, and CAD [ 5 , 6 , 7 , 8 , 15 ]. In this study, we found that the rs580253 A and rs501192 A alleles of the CASP1 gene, as well as the gene–gene interaction between BAT1 , NFKBIL1 , LTA , and CASP1 , were associated with an increased risk of developing restenosis after coronary stenting.…”

“…As a result, 66 patients were placed in the restenosis group and 153 patients in the non-restenosis group. As a comparison group, we included 625 healthy individuals with neither symptoms nor previous diagnosis of cardiovascular or systemic disease previously reported [ 5 , 15 ]. All subjects were considered Mexican mestizos and ethnically matched according to ancestry informative markers (AIMs) in the ADMIXTURE software.…”

“…Previous work has shown that the proteins encoded by the branched-chain amino-acid transaminase 1 ( BAT1 ), NF-kB inhibitor-like-1 ( NFKBIL1 ), lymphotoxin-alpha (LTA), and Caspase-1 ( CASP1 ) genes play an important role in the regulation of inflammatory process and atherosclerotic plaque development [ 5 , 6 , 7 , 8 ]. BAT1 encodes a nuclear protein called HLA-B-associated transcript 1, which downregulates the expression of pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) [ 9 , 10 ].…”

“…The BAT1 , NFKBIL1 , and LTA genes are located in the 6q21.3 region. Recent evidence has shown an association between three polymorphisms of these genes [ BAT1 rs2239527 C/G, NFKBIL1 rs2071592 T / A , and LTA rs1800683 A / G ] with the presence of acute coronary syndrome (ACS), myocardial infarction, and hypertension [ 5 , 6 , 7 , 8 ]. On the other hand, the CASP1 gene is located on chromosome 11q23 and presents two relevant polymorphisms [rs501192 A / G and rs580253 A / G ] associated with ACS [ 15 ].…”

Research progress on branched-chain amino acid aminotransferases

“…BCAT has also been studied in cardiovascular diseases. BCAA aminotransferase 1-23C/G polymorphisms have been found to have a protective effect against acute coronary syndrome, but the specific mechanism has not been studied (Ramírez-Bello et al, 2020). Activation of BCAT1 and inhibition of oxoeicosanoid receptor can reduce acute myocardial infarction (Lai et al, 2021).…”