Functional Analysis LRP6 Novel Mutations in Patients with Coronary Artery DiseaseReport as inadecuate

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Genetic architecture of coronary artery disease CAD is still to be defined. Since low density lipoprotein receptor-related protein 6 LRP6 gene play critical roles in Wnt signal transduction which are important for vascular development and endodermis specification, we therefore resequenced it to search for mutations in CAD patients.


We systemically sequenced all the exons and promoter region of LRP6 gene in a sample of 380 early onset CAD patients and 380 control subjects in Chinese.


In total, we identified 5 patient-specific mutations including K82N two patients, S488Y one patient, P1066T two patients, P1206H two patients and I1264V one patient All these mutations located at the extracellular domain of LRP6 gene. In vitro functional analysis of patient-specific mutations demonstrated that these mutations resulted in a significant reduction in both protein level transporting to cell membrane and downstream Wnt signal activity. Furthermore, we found that LRP6 novel mutations attenuated proliferation and migration of human umbilical vein endothelial cells HUVECs when compared with wild type WT LRP6.


Our results demonstrated that these loss-of-function variants might contribute to disease liability in a subset of CAD and defects in Wnt signal activation might be important contributing factors for the onset of CAD.

Author: Yujun Xu , Wei Gong , Jia Peng, Haoran Wang, Jin Huang, Hu Ding , Dao Wen Wang



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