Zhang Yuhui, Wang Yunhong, Zhai Mei, Gan Tianyi, Zhao Xuemei, Zhang Rongcheng, An Tao, Huang Yan, Zhou Qiong, Zhang Jian
State Key Laboratory of Cardiovascular Disease, Heart Failure Center Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
State Key Laboratory of Cardiovascular Disease, Heart Failure Center Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Gene. 2018 Feb 5;642:293-298. doi: 10.1016/j.gene.2017.11.026. Epub 2017 Nov 10.
Galectin-3 plays an important role in modulating cardiac inflammation and fibrosis. It also takes part in the pathways underlying cardiac remodeling. Therefore, LGALS3 gene, encoding galectin-3 protein, is a promising candidate for the genetic study of dilated cardiomyopathy (DCM). To date, there has been no research evaluating the association between LGALS3 gene polymorphisms and the susceptibility and prognosis of DCM.
Genotyping of 4 single nucleotide polymorphisms (SNPs) in the LGALS3 gene, which were reported to be functional in the literature, was performed in 279 unrelated clinically diagnosed DCM patients and 363 apparently healthy controls from Northern Han Chinese population using iPLEX SNP Genotyping analysis on a Sequenom MassARRAY System. The frequency of G allelic polymorphism of rs1009977 and the C allelic polymorphism of rs4652 were lower in DCM patients (OR=0.77, 95% CI [0.60-0.99], P=0.045; OR=0.79, 95% CI [0.63-0.99], P=0.042, respectively). The minor variants of rs1009977 and rs4652 were associated with low susceptibility of DCM under additive genetic models (P=0.045 and P=0.040, respectively). The AA genotype of both rs2274273 and rs4644 was associated with lower left ventricular ejection fraction (recessive model, P=0.018 for both; additive model, P=0.039 for both). The G variant of rs1009977 was related with lower serum galectin-3 level in DCM patients under three genetic models (additive model, P=0.020, dominant model, P=0.020, recessive model, P=0.037). The A variant of both rs2274273 and rs4644 was associated with lower level of galectin-3 in DCM patients under additive model (P=0.032 for both) and dominant model (P=0.012 for both). None of the 4 SNPs was associated with the cardiovascular or all-cause death rate of DCM. In Conclusion, LGALS3 gene polymorphisms might be associated with the susceptibility of DCM in a Northern Han Chinese population.
半乳糖凝集素-3在调节心脏炎症和纤维化中起重要作用。它还参与心脏重塑的潜在通路。因此，编码半乳糖凝集素-3蛋白的LGALS3基因是扩张型心肌病（DCM）基因研究的一个有前景的候选基因。迄今为止，尚无研究评估LGALS3基因多态性与DCM易感性及预后之间的关联。
使用Sequenom MassARRAY系统上的iPLEX SNP基因分型分析，对279例无亲缘关系的临床诊断DCM患者和363例来自中国北方汉族人群的明显健康对照进行了LGALS3基因中4个单核苷酸多态性（SNP）的基因分型，这些SNP在文献中被报道具有功能。DCM患者中rs1009977的G等位基因多态性频率和rs4652的C等位基因多态性频率较低（OR分别为0.77，95%CI[0.60-0.99]，P=0.045；OR为0.79，95%CI[0.63-0.99]，P=0.042）。在加性遗传模型下，rs1009977和rs4652的次要变异与DCM的低易感性相关（分别为P=0.045和P=0.040）。rs2274273和rs4644的AA基因型均与较低的左心室射血分数相关（隐性模型，两者均为P=0.018；加性模型，两者均为P=0.039）。在三种遗传模型下，rs1009977的G变异与DCM患者较低的血清半乳糖凝集素-3水平相关（加性模型，P=0.020，显性模型，P=0.020，隐性模型，P=0.037）。在加性模型（两者均为P=0.032）和显性模型（两者均为P=0.012）下，rs2274273和rs4644的A变异均与DCM患者较低的半乳糖凝集素-3水平相关。这4个SNP均与DCM的心血管或全因死亡率无关。结论：LGALS3基因多态性可能与中国北方汉族人群DCM的易感性相关。
