Djordjevic Ana, Dekleva Milica, Zivkovic Maja, Stankovic Aleksandra, Markovic Nikolic Natasa, Alavantic Dragan, Djuric Tamara
"VINCA" Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, P.O.Box 522, 11001, Belgrade, Serbia.
Department of Cardiology, University Clinical Center "Zvezdara", Belgrade, Serbia.
Mol Biol Rep. 2018 Dec;45(6):2227-2236. doi: 10.1007/s11033-018-4384-4. Epub 2018 Sep 18.
Post-infarct left ventricular remodeling (LVR) process increases the risk of heart failure (HF). Circulating galectin-3 has been associated with fibrosis, inflammation and cardiac dysfunction during the remodeling process after myocardial infarction (MI). The aims of this prospective case study were to investigate the association of potentially functional variants in the vicinity of LGALS-3 locus, rs2274273 and rs17128183 with maladaptive LVR and whether these variants could affect LGALS-3 mRNA expression in peripheral blood mononuclear cells of patients 6 months after the first MI. This study encompassed 167 patients with acute MI that were followed up for 6 months. Evidence of LVR was obtained by repeated 2D Doppler echocardiography. Rs2274273, rs17128183 and LGALS-3 mRNA expression were detected by TaqMan technology. Rs2274273 and rs17128183 rare allele bearing genotypes, according to the dominant model (CT+TT vs. CC and AG+GG vs. AA, respectively), were significantly and independently associated with maladaptive LVR (adjusted OR = 3.02, P = 0.016; adjusted OR = 3.14, P = 0.019, respectively) and higher LGALS-3 mRNA expression (fold induction 1.203, P = 0.03 and 1.214, P = 0.03, respectively). Our exploratory results suggest that rs2274273 and rs17128183 variants affect LGALS-3 mRNA and bear the risk for maladaptive LVR post-MI remodeling. Further replication and validation in a larger group of patients is inevitable.
心肌梗死后左心室重构（LVR）过程会增加心力衰竭（HF）的风险。循环半乳凝素-3与心肌梗死（MI）后重构过程中的纤维化、炎症及心脏功能障碍相关。本前瞻性病例研究的目的是调查LGALS - 3基因座附近潜在功能性变体rs2274273和rs17128183与适应性不良的LVR之间的关联，以及这些变体是否会影响首次MI后6个月患者外周血单个核细胞中LGALS - 3 mRNA的表达。本研究纳入了167例急性MI患者，并对其进行了6个月的随访。通过重复二维多普勒超声心动图获得LVR的证据。采用TaqMan技术检测rs2274273、rs17128183和LGALS - 3 mRNA的表达。根据显性模型，rs2274273和rs17128183携带罕见等位基因的基因型分别与适应性不良的LVR显著且独立相关（校正OR = 3.02，P = 0.016；校正OR = 3.14，P = 0.019），且与更高的LGALS - 3 mRNA表达相关（倍数诱导分别为1.203，P = 0.03和1.214，P = 0.03）。我们的探索性结果表明，rs2274273和rs17128183变体影响LGALS - 3 mRNA，并在MI后重构中承担适应性不良LVR的风险。在更大规模的患者群体中进行进一步的重复和验证是必要的。
