Department of Radiobiology and Molecular Genetics, "Vinca" Institute of Nuclear Sciences-National Institute of the Republic of Serbia, Mike Petrovica Alasa 12-14, P.O. Box 522, University of Belgrade, Belgrade 11001, Serbia.
Department of Radiobiology and Molecular Genetics, "Vinca" Institute of Nuclear Sciences-National Institute of the Republic of Serbia, Mike Petrovica Alasa 12-14, P.O. Box 522, University of Belgrade, Belgrade 11001, Serbia.
J Stroke Cerebrovasc Dis. 2022 Jan;31(1):106212. doi: 10.1016/j.jstrokecerebrovasdis.2021.106212. Epub 2021 Nov 20.
Galectin-3 affects a variety of biological processes. It is encoded by LGALS-3, located in unique haplotype block in Caucasians. Most of the studies regarding the gal-3 role in atherosclerosis are focused exclusively on protein/mRNA levels. Genetic analyses of LGALS-3 are scarce. We sought to thoroughly examine the genetic background of gal-3 and to analyze tag variants that cover more than 80% variability of the LGALS-3 containing hap-block in association with carotid plaque presence (CPP). According to Tagger server, rs4040064 G/T, rs11628437 G/A and rs7159490 C/T cover 82% (r > 0.8) of the genetic variance of this hap-block. Our aims were to investigate possible association of rs4040064, rs11628437 and rs7159490 haplotypes with CPP in patients with advanced carotid atherosclerosis (CA) and to analyze their possible effect on LGALS-3 mRNA expression in carotid plaques.
Study group consisted of 468 patients and 296 controls. Rs4040064, rs11628437, rs7159490 and LGALS-3 mRNA expression were detected by TaqMan® technology.
We have found that haplotype TAC was associated with the cerebrovascular insult (CVI) occurrence (OR = 1.68, 95% CI = 1.09-2.58, p = 0.02), compared to the referent haplotype. OR was adjusted for hypertension, age and BMI. TAC also showed higher, but not statistically significant, LGALS-3 expression in carotid plaques.
Our results suggest that rs4040064, rs11628437 and rs7159490 bear no association with CPP, neither they affect LGALS-3 mRNA in carotid plaques. However, we showed a significant association of haplotype TAC with the CVI occurrence in CA patients from Serbia. Replication and validation of our results are required.
半乳糖凝集素-3 影响多种生物学过程。它由 LGALS-3 编码，位于高加索人中独特的单倍型块中。大多数关于半乳糖凝集素-3 在动脉粥样硬化中的作用的研究都仅集中在蛋白质/信使 RNA 水平上。LGALS-3 的遗传分析很少。我们试图彻底研究半乳糖凝集素-3 的遗传背景，并分析覆盖 LGALS-3 所含 haploblock 超过 80%变异性的标记变体与颈动脉斑块存在（CPP）的关联。根据 Tagger 服务器，rs4040064 G/T、rs11628437 G/A 和 rs7159490 C/T 覆盖该 haploblock 遗传变异的 82%（r>0.8）。我们的目的是研究 rs4040064、rs11628437 和 rs7159490 单倍型与颈动脉粥样硬化（CA）患者 CPP 之间可能的关联，并分析它们对半乳糖凝集素-3 在颈动脉斑块中 mRNA 表达的可能影响。
研究组包括 468 名患者和 296 名对照。通过 TaqMan®技术检测 rs4040064、rs11628437、rs7159490 和 LGALS-3 mRNA 表达。
我们发现，与参考单倍型相比，TAC 单倍型与脑血管事件（CVI）的发生（OR=1.68，95%CI=1.09-2.58，p=0.02）相关。OR 经高血压、年龄和 BMI 调整。TAC 还显示颈动脉斑块中半乳糖凝集素-3 的表达更高，但无统计学意义。
我们的结果表明，rs4040064、rs11628437 和 rs7159490 与 CPP 无关，也不影响颈动脉斑块中的 LGALS-3 mRNA。然而，我们显示塞尔维亚 CA 患者的 TAC 单倍型与 CVI 发生之间存在显著关联。需要复制和验证我们的结果。
