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Genetic determinants of circulating galectin-3 levels in patients with coronary artery disease.

ABSTRACT: BACKGROUND:Galectin-3 plays a crucial role in the regulation of inflammation. The aim of this study was to elucidate the association between LGALS3 genotypes, galectin-3 levels, and inflammatory marker levels in patients with coronary artery disease (CAD). RESULTS:A total of 474 patients with CAD were enrolled. Significant correlations were discerned between galectin-3 levels and leukocyte counts, C-reactive protein, soluble intercellular adhesion molecule-1, and matrix metalloproteinase 9 levels (all p < .05). The LGALS3 rs2274273, rs4644, rs4652 genotypes, and haplotypes CAC, CCC, and ACT exhibited a significant association with galectin-3 levels (for genotypes, p = 1.05 × 10-25 , 3.54 × 10-25 , and 2.74 × 10-7 , respectively). Multivariate analysis showed LGALS3 rs2274273 and rs4644 genotypes contributing to 20.8% variation of galectin-3 levels. However, there was no association between LGALS3 genotypes and other inflammatory marker levels. CONCLUSIONS:Our data showed strong genetic determinants of galectin-3 levels in patients with CAD. The galectin-3 levels, but not LGALS3 genotypes, were associated with multiple inflammatory marker levels. Further study may be necessary to elucidate the molecular mechanism of galectin-3 in the pathogenesis of chronic inflammatory disorders.

SUBMITTER: Liao YH

PROVIDER: S-EPMC7507567 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Genetic determinants of circulating galectin-3 levels in patients with coronary artery disease.

Liao Yu-Huang YH Teng Ming-Sheng MS Juang Jyh-Ming J JJ Chiang Fu-Tien FT Er Leay-Kiaw LK Wu Semon S Ko Yu-Lin YL

Molecular genetics & genomic medicine 20200623 9

<h4>Background</h4>Galectin-3 plays a crucial role in the regulation of inflammation. The aim of this study was to elucidate the association between LGALS3 genotypes, galectin-3 levels, and inflammatory marker levels in patients with coronary artery disease (CAD).<h4>Results</h4>A total of 474 patients with CAD were enrolled. Significant correlations were discerned between galectin-3 levels and leukocyte counts, C-reactive protein, soluble intercellular adhesion molecule-1, and matrix metallopro ...[more]

PMID: 32573962

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Project description:BackgroundThe relationship between galectin-3 (Gal-3) and coronary artery disease (CAD) has not been fully elucidated.AimThis study aimed to determine the relationship between the presence and severity of CAD and serum Gal-3 levels.Patients and methodsThree-hundred thirty-one consecutive CAD patients were enrolled as the study group. An additional 62 patients without CAD were enrolled as the control group. Serum Gal-3 levels were separately compared between the non-CAD and CAD groups, among the stable CAD and Acute coronary syndrome (ACS) groups, and between CAD patients with low and high SYNTAX scores (SSs). The 1-year cumulative rate of major adverse cardiac events (MACEs) was also compared among ACS patients by Gal-3 levels.ResultsSerum Gal-3 was significantly higher in the CAD group than in the non-CAD group 3.89 (0.16-63.67) vs. 2.07 (0.23-9.38) ng/ml, P < 0.001. Furthermore, serum Gal-3 was significantly higher in the non-ST-segment elevation ACS (NSTE-ACS) group than that in the stable CAD group, 4.72 (1.0-16.14) vs. 2.23 (0.65-23.8) ng/ml, P = 0.04 and higher in the ST-segment elevation myocardial infarction (STEMI) group than that in the stable CAD group 7.87 (0.59-63.67) vs. 2.23 (0.65-23.8) ng/ml, P < 0.001. Serum Gal-3 level was an independent predictor of ACS compared with stable CAD group (OR = 1.131, 95% CI: 1.051-1.217, P = 0.001) as well as high SS (OR = 1.030, 95% CI: 1.021-1.047, P = 0.038) after adjust other confounding risk factors. Acute coronary syndrome patients with Gal-3 levels above the median (gal-3 = 4.78 ng/ml) showed a higher cumulative MACE rate than those with Gal-3 levels below the median. After adjusting other confounding risk factors, Gal-3 remained an independent risk factor for the cumulative rate of MACEs in ACS patients (6% higher rate of MACEs incidence per 1 ng/ml increment of Gal-3).ConclusionGalectin-3 correlated with the presence of CAD as well as coronary stability and complexity. Galectin-3 may be valuable in predicting mid-term prognosis in ACS patients.

Project description:Monocytes and T-cells play an important role in the development of atherosclerotic coronary artery disease (CAD). Differences in transcriptional activity of these cells might reflect the individual's atherosclerotic burden. Transcriptome analysis of circulating mononuclear cells from carefully matched atherosclerotic and control patients will potentially provide insights into the pathophysiology of atherosclerosis and supply biomarkers for diagnostic purposes. From patients undergoing coronary angiography because of anginal symptoms, we carefully matched 18 patients with severe triple-vessel CAD to 13 control patients without signs of CAD on angiography. All patients were on statin and aspirin treatment. RNA from circulating CD4+ T-cells, CD14+ monocytes, lipopolysaccharide-stimulated monocytes, macrophages and CD34+ progenitor cells was subjected to genome-wide expression analysis. Only CD14+ monocytes demonstrated that a small number of genes involved in activation was overexpressed in control patients, which was verified by real-time polymerase-chain reaction. In this pilot study, cautious matching of patients with severe atherosclerotic CAD with control patients without angiographic signs of coronary atherosclerosis did not reveal differences in transcriptional activity in four out of five different mononuclear cell types. In resting monocytes from patients without overt CAD some inflammatory genes were overexpressed as compared to patients with severe CAD. Large inter-individual variability prevented the use of single differentially expressed genes as biomarkers. Keywords: disease-state analysis In total 153 arrays were analyzed with 6 technical replicates (147 biological samples). CD34+ stem cells, CD4+ T-cells, resting CD14+ monocytes, stimulated monocytes and macrophages were analyzed, all from patient with severe coronary atherosclerosis or controls that had no coronary atherosclerosis as determined angiographically, and which were carefully matched for age and gender.

Dataset Information

Genetic determinants of circulating galectin-3 levels in patients with coronary artery disease.

Publications

Genetic determinants of circulating galectin-3 levels in patients with coronary artery disease.

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