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变异标签 与急性事件后 6 个月首次心肌梗死和血浆半乳糖凝集素-3 相关的单倍型块。

Variants Tagging Haplotype Block in Association with First Myocardial Infarction and Plasma Galectin-3 Six Months after the Acute Event.

机构信息

Department of Radiobiology and Molecular Genetics, "Vinca" Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, Serbia.

Department of Cardiology, University Clinical Centre "Zvezdara", 11120 Belgrade, Serbia.

出版信息

Genes (Basel). 2022 Dec 29;14(1):109. doi: 10.3390/genes14010109.

DOI:10.3390/genes14010109
PMID:36672849
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9859409/
Abstract

Galectin-3 is encoded by , located in a unique haplotype block in Caucasians. According to the Tagger server, rs4040064, rs11628437, and rs7159490 cover 82% (r > 0.8) of the genetic variance of this HapBlock. Our aims were to examine the association of their haplotypes with first myocardial infarction (MI), changes in left ventricular echocardiographic parameters over time, and impact on plasma galectin-3 and mRNA in peripheral blood mononuclear cells, both 6 months post-MI. The study group consisted of 546 MI patients and 323 controls. Gene expression was assessed in 92 patients and plasma galectin-3 in 189 patients. Rs4040064, rs11628437, rs7159490, and mRNA expression were detected using TaqMan technology. Plasma galectin-3 concentrations were determined by the ELISA method. We found that the TGC haplotype could have a protective effect against MI (adjusted OR 0.19 [0.05-0.72], = 0.015) and that the GAC haplotype had significantly higher galectin-3 concentrations (48.3 [37.3-59.4] ng/mL vs. 18.9 [14.5-23.4] ng/mL, < 0.0001), both in males and compared to the referent haplotype GGC. Higher plasma Gal-3 was also associated with higher NYHA class and systolic dysfunction. Our results suggest that variants tagging HapBlock could reflect plasma Gal-3 levels 6 months post-MI and may have a potential protective effect against MI in men. Further replication, validation, and functional studies are needed.

摘要

半乳糖凝集素-3 由 编码,位于高加索人群中的独特单倍型块中。根据 Tagger 服务器,rs4040064、rs11628437 和 rs7159490 覆盖了该 HapBlock 遗传变异的 82%(r > 0.8)。我们的目的是研究其单倍型与首次心肌梗死(MI)、随时间变化的左心室超声心动图参数变化以及对 MI 后 6 个月外周血单个核细胞中血浆半乳糖凝集素-3 和 mRNA 的影响之间的关联。研究组包括 546 名 MI 患者和 323 名对照。对 92 名患者进行了基因表达评估,对 189 名患者进行了血浆半乳糖凝集素-3 评估。使用 TaqMan 技术检测 rs4040064、rs11628437、rs7159490 和 mRNA 的表达。通过 ELISA 法测定血浆半乳糖凝集素-3 浓度。我们发现,TGC 单倍型可能对 MI 有保护作用(调整后的 OR 0.19 [0.05-0.72], = 0.015),并且 GAC 单倍型的半乳糖凝集素-3 浓度明显更高(48.3 [37.3-59.4] ng/mL 与 18.9 [14.5-23.4] ng/mL, < 0.0001),无论是男性还是与参照单倍型 GGC 相比。较高的血浆 Gal-3 也与较高的 NYHA 分级和收缩功能障碍相关。我们的研究结果表明,标记 HapBlock 的变体可能反映 MI 后 6 个月的血浆 Gal-3 水平,并且可能对男性 MI 具有潜在的保护作用。需要进一步的复制、验证和功能研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b10/9859409/e51a891d1a28/genes-14-00109-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b10/9859409/64476300df18/genes-14-00109-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b10/9859409/e51a891d1a28/genes-14-00109-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b10/9859409/64476300df18/genes-14-00109-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b10/9859409/e51a891d1a28/genes-14-00109-g002.jpg

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